The Lasting Health Burdens of Tuberculosis

Increased Health Risks for Tuberculosis (TB) Survivors:

• Higher likelihood of recurrent TB and increased all-cause mortality, regardless of treatment adequacy.
• Increased risk of chronic respiratory diseases; many survivors experience abnormal spirometry, chronic symptoms, and impaired lung function (e.g., low forced vital capacity, reduced forced expiratory volume).
• Elevated risk of mortality, cardiovascular disease, and hospitalizations due to respiratory issues.
• Reduction in health-related quality of life, exercise tolerance, and increased social stigma and economic challenges post-treatment.

Social and Economic Impacts:

• Persistent social stigma, leading to isolation, diminished marriage prospects, and potential divorce.
• Financial strain from medical costs and income loss during treatment, deepening poverty and potentially affecting family members (e.g., malnutrition or disrupted education for children).

Population and Disability Burden:

• Estimated 155 million TB survivors alive in 2020, a population exceeding the number of new cases annually.
• Many survivors experience post-recovery disability, significantly impacting TB morbidity estimates.

Healthcare Needs and Interventions:

• Complex health needs requiring a multidisciplinary approach, involving TB programs and non-communicable disease clinics.
• Recommended interventions include lung function evaluation and treatments (e.g., bronchodilators, antibiotics, steroid therapy) for managing chronic respiratory morbidity.
• In low-resource settings, interventions like pneumococcal vaccination, pulmonary rehabilitation, and smoking cessation promotion improve quality of life.

Impact on Childhood Survivors:

• Childhood TB can result in lifelong lung function impairment, underscoring the need for early prevention and diagnosis.
• Approximately 12% of post-TB life-years lost are due to childhood TB, emphasizing the need for protective measures to support lung growth and capacity.

Financial Impact and Social Support:

• Many TB patients are economically vulnerable, with treatment costs often causing catastrophic, long-term financial strain.
• Social protection programs (e.g., financial, food, housing support) could alleviate these effects and reduce treatment-related costs.

Need for Further Research:

• Critical need for large, prospective studies to understand post-TB lung damage, long-term morbidity effects, and targeted treatments.
• Future trials should evaluate the impact of therapies on post-treatment morbidity, not just microbiological cure, to enhance long-term outcomes for survivors.

Association Between Diabetes Mellitus (DM) and Multidrug-Resistant TB (MDR-TB):

• Significant association between DM and MDR-TB; TB patients without DM have a lower risk of MDR-TB than those with DM.
• Contributing factors include impaired immune function, altered microbial genomics, uncontrolled glucose levels, and compromised immune responses (e.g., reduced chemotactic response, oxidative species).
• Higher likelihood of treatment non-adherence and elevated treatment failure rates in TB patients with DM.

Type 2 Diabetes Mellitus (T2DM) and Risk Factors:

• Most common form of diabetes, representing 90-95% of cases, especially in low- and middle-income countries.
• Strong associations with overweight, obesity (particularly visceral fat), aging, alcohol use, ethnicity, and family history.
• T2DM stems from genetic predisposition and environmental triggers; obesity-related insulin resistance is a key precursor.

Natural Infection and Immune Response to TB:

• Infection through inhalation of Mtb-containing aerosols, which settle in the alveoli, leading to invasion of macrophages.
• Initial immune responses involve macrophages and the secretion of antigens to activate T-cell proliferation.
• Failure to control Mtb can result in primary active TB, while containment without elimination leads to latent TB infection (LTBI).

T2DM as a Risk Factor for Mtb Infection:

• T2DM patients have a significantly higher risk of LTBI and active TB development, including multi-drug resistance.
• Higher rates of extensive lung lesions, cavities, and adverse outcomes, such as increased mortality, observed in T2DM-TB patients.

Impaired Immunity in T2DM and TB:

• T2DM patients show reduced macrophage and neutrophil function, affecting the immune response to Mtb.
• Chronic inflammation and immune cell imbalances further compromise immune effectiveness, increasing TB susceptibility.

T Cell and Cytokine Imbalance in ATB-T2DM Patients:

• Imbalance in T cell populations (e.g., elevated Th2 and Th17 cells, reduced Th1), impaired cytokine production, and increased IL-10 inhibit the Th1 response.
• This immunosuppression lowers the body’s ability to control Mtb infection effectively.

Metabolic and Microbiome Changes in ATB-T2DM Patients:

• Elevated biomarkers and amino acid levels are potential indicators for TB diagnosis.
• T2DM-related gut microbiome changes can impact immune responses and are exacerbated by TB, reducing microbial diversity.

Observational Studies on Diabetes and PTB:

• Limitations include reverse causality, confounding factors, and lack of diabetes phenotype specificity.
• Clinical recommendations suggest managing both T1DM and HDL-C levels to improve outcomes for patients with PTB.

LTBI Incidence in Healthcare Workers (Brunei Darussalam):

• Annual incidence rate in government sector healthcare workers: 8.1 to 24.6, averaging 14.6 over four years.
• Treatment acceptance shows a significant difference based on gender, with females demonstrating higher acceptance.

References:

1. Dodd, P.J., Yuen, C.M., Jayasooriya, S.M., van der Zalm, M.M. and Seddon, J.A., 2021. Quantifying the global number of tuberculosis survivors: a modelling study. The Lancet Infectious Diseases, 21(7), pp.984-992.
2. Rehman Au, Khattak M, Mushtaq U, Latif M, Ahmad I, Rasool MF, Shakeel S, Hayat K, Hussain R, Alhazmi GA, Alshomrani AO, Alalawi MI, Alghamdi S, Imam MT, Almarzoky Abuhussain SS, Khayyat SM and Haseeb A (2023) The impact of diabetes mellitus on the emergence of multi-drug resistant tuberculosis and treatment failure in TB-diabetes comorbid patients: a systematic review and meta-analysis. Front. Public Health 11:1244450.
3. Ssekamatte P, Sande OJ, van Crevel R and Biraro IA (2023). Immunologic, metabolic and genetic impact of diabetes on tuberculosis susceptibility. Front. Immunol. 14:1122255. See also: Lin TB Lab
4. Jiang, Y., Zhang, W., Wei, M., Yin, D., Tang, Y., Jia, W., Wang, C., Guo, J., Li, A. and Gong, Y., 2024. Associations between type 1 diabetes and pulmonary tuberculosis: a bidirectional mendelian randomization study. Diabetology & Metabolic Syndrome, 16(1), pp.1-9.
5. Syafiq, N.J.M., Trivedi, A.A., Lai, A., Fontelera, M.P.A. and Lim, M.A., 2023. Latent tuberculosis infection in health-care workers in the government sector in Brunei Darussalam: A cross-sectional study. Journal of Integrative Nursing, 5(3), pp.197-202.

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A Comprehensive Approach to TB Control in Diabetic Populations

1. Background

• Type 2 Diabetes Mellitus (DM2) is a recognized risk factor for Tuberculosis (TB) due to impaired host immunity, especially in settings with high TB prevalence.

• Studying this relationship is complex because of global population heterogeneity, including differences in:

  • Age, access to medical care, glucose control levels.

  • Types and numbers of complications, and medications available.

2. Key Findings

• Military Personnel: Higher prevalence and more rapid cumulative risk of recurrent TB in those with DM2 compared to those without.

• Geographic and Occupational Risks: In resource-limited settings (e.g., Peru), military personnel with DM2 may face additional risk due to fieldwork exposure.

• Sex-Based Differences: DM is associated with a higher TB recurrence risk in men, potentially due to factors like smoking and impaired immunity, though no significant association in women.

• Glycemic Control: Poor glycemic control, higher fasting plasma glucose (FPG), and elevated HbA1c levels are associated with cavity formation, sputum positivity, and extensive lesions in TB-DM patients.

3. Risk Factors and Confounders

• Risk Factors: Age, sex, and glycemic control at admission influence cavity formation. FPG levels at admission and discharge are associated with lesion location and HbA1c levels.

• Confounders: Smoking, alcohol use, and chronic obstructive pulmonary disease (COPD) may exacerbate TB severity and recurrence, particularly among male DM patients.

4. Screening and Cost Efficiency

• Mass Screening: While feasible, mass TB screening among persons with diabetes (PWD) may not be cost-efficient due to low detection rates. High costs are largely driven by diabetes management rather than TB-related expenses.

• Targeted Screening: More efficient in populations with high TB incidence (≥100 cases per 100,000). A risk-stratified approach could be practical in low to medium TB burden areas.

• Symptom Screening: Insufficient alone, necessitating comprehensive methods to detect TB among PWD.

5. TB Control Frameworks and Strategies

• DOTS (Directly Observed Treatment, Short-Course):

  • A public health strategy that includes:

    • Political commitment, case detection, short-course chemotherapy with patient support, reliable drug supplies, and standardized outcome reporting.

• MDG Framework:

  • Focuses on DOTS with case detection and treatment success metrics, along with broader impact measures (incidence, prevalence, deaths).

  • Emphasizes comprehensive TB control and epidemiological evaluation beyond DOTS.

• Comprehensive TB Approach:

  • Prevention and improved patient care, especially among patients with HIV or drug-resistant TB.

  • Integration of new technologies and optimization of existing tools.

6. Regional Challenges and DOTS Expansion

• Regional Challenges: Africa and Eastern Europe face unique TB challenges due to HIV/AIDS and drug resistance, requiring tailored solutions.

• DOTS Limitations: By 2003, DOTS had nearly exhausted its public health utility, necessitating adaptations for non-public facilities and professional healthcare expansion to underserved areas.

7. Mortality and Incidence Measurement

• Mortality Statistics: Accurate TB death records are often unavailable in low-income countries due to inadequate vital registration systems.

• Incidence Rates: Rarely measured directly; usually estimated from population surveys or surveillance system assessments, though these methods have accuracy limitations.

Sources:

1. Alvarado-Valdivia, N.T., Flores, J.A., Inolopú, J.L. and Rosales-Rimache, J.A., 2024. Type 2 diabetes mellitus and recurrent Tuberculosis: A retrospective cohort in Peruvian military workers. Journal of Clinical Tuberculosis and Other Mycobacterial Diseases, 35, p.100432.

2. Dye, C., Watt, C.J., Bleed, D.M., Hosseini, S.M. and Raviglione, M.C., 2005. Evolution of tuberculosis control and prospects for reducing tuberculosis incidence, prevalence, and deaths globally. Jama, 293(22), pp.2767-2775. 

3. Liu, Q., You, N., Wen, J., Wang, J., Ge, Y., Shen, Y., Ding, X., Lu, P., Chen, C., Zhu, B. and Zhu, L., 2023. Yield and efficiency of a population-based mass tuberculosis screening intervention among persons with diabetes in Jiangsu Province, China. Clinical Infectious Diseases, 77(1), pp.103-111. 

4. Meng F, Lan L, Wu G, Ren X, Yuan X,Yang M, Chen Q, Peng X and Liu D (2023). Impact of diabetes itself and glycemic control status on tuberculosis. Front. Endocrinol. 14:1250001.

5. Eksombatchai, D., Jeong, D., Mok, J., Jeon, D., Kang, H.Y., Kim, H.J., Kim, H.S., Choi, H. and Kang, Y.A., 2023. Sex differences in the impact of diabetes mellitus on tuberculosis recurrence: a retrospective national cohort study. International Journal of Infectious Diseases, 127, pp.1-10.

See also: https://tbreadingnotes.blogspot.com/2024/10/impact-of-diabetes-itself-and-glycemic.html

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