TB Diagnostic Technologies

· TB Diagnostic Technologies and Hospital Impact

• Medical Center A in Taipei transitioned to auramine-rhodamine staining from Ziehl-Neelsen staining by 2014, aiming to improve TB detection and patient isolation.
• Enhanced diagnostic sensitivity resulted in doubling the positive sputum smear rate from 22.8% to 48.1%, especially for non-cavitary lung lesions.
• The median duration of non-isolated infectiousness reduced significantly from 12.5 days to 3 days, and the total number of non-isolated infectious patient-days decreased by 69% from 2001 to 2014.
• Suggestion: Implement continuous training for healthcare staff on the latest TB diagnostic technologies to maintain high detection rates and reduce the time to isolation.

· Risk Factors and Control Measures in Healthcare Settings

• Inadequate ventilation and insufficient environmental cleaning in healthcare settings heighten TB transmission risks.
• Frequent healthcare visits are closely linked to increased TB incidence, necessitating robust infection control measures in high-traffic areas like internal medicine and family medicine.
• Suggestion: Prioritize the installation of germicidal ultraviolet systems and upgraded ventilation in outpatient areas to minimize airborne transmission.

· Epidemiological Insights and Trends

• TB incidence and related mortality have declined in younger populations (<20 and 20–50 years) in mainland China, reflecting effective control measures.
• However, SS- TB cases and mortality in the >50 age group remained high, indicating ongoing vulnerabilities.
• Suggestion: Develop targeted health campaigns and screening programs focused on the elderly to address the persistently high TB rates in this demographic.

· Regional and Systemic Challenges in Taiwan

• Increased Health System Delay (HSD) in diagnosing TB was noted between 2003 and 2008, influenced by factors such as patient’s age, gender, and the type of health facility visited.
• Eastern Taiwan showed shorter HSDs due to a higher concentration of TB-specialized providers, while medical centers experienced longer delays.
• Suggestion: Enhance the distribution and accessibility of specialized TB healthcare services across different regions to ensure timely diagnosis and treatment.

· Link Between TB and Chronic Conditions

• Tuberculosis is a significant risk factor for developing chronic obstructive pulmonary disease (COPD), with risks increasing due to delays in TB treatment initiation.
• Early diagnosis and timely treatment of TB are crucial to mitigate COPD risk.
• Suggestion: Strengthen the integration of TB and COPD management protocols to improve patient outcomes and reduce the incidence of COPD among former TB patients.

See also: https://lintblab.weebly.com

References:

1. Sun H-Y, Wang J-Y, Chen Y-C, Hsueh PR, Chen Y-H, Chuang Y-C, et al. (2020) Impact of introducing fluorescent microscopy on hospital tuberculosis control: A before-after study at a high caseload medical center in Taiwan. PLoS ONE 15(4): e0230067.
2. Pan, S.C., Chen, C.C., Chiang, Y.T., Chang, H.Y., Fang, C.T. and Lin, H.H., 2016. Health care visits as a risk factor for tuberculosis in Taiwan: a population-based case–control study. American journal of public health, 106(7), pp.1323-1328.
3. Liu, K.H., Xiao, Y.X. and Jou, R., 2024. Multidrug-resistant tuberculosis clusters and transmission in Taiwan: a population-based cohort study. Frontiers in Microbiology, 15, p.1439532.
4. Huang, F. and Bello, S.T., 2024. Spatiotemporal analysis of regional and age differences in tuberculosis prevalence in mainland China. Tropical Medicine & International Health, 29(9), pp.833-841.
5. Fu, H., Lin, HH., Hallett, T.B. et al. Explaining age disparities in tuberculosis burden in Taiwan: a modelling study. BMC Infect Dis 20, 191 (2020).
6. Chen, C.C., Chiang, C.Y., Pan, S.C., Wang, J.Y. and Lin, H.H., 2015. Health system delay among patients with tuberculosis in Taiwan: 2003–2010. BMC infectious diseases, 15, pp.1-9.
7. Lee C-H, Lee M-C, Lin H-H, Shu C-C, Wang J-Y, et al. (2012) Pulmonary Tuberculosis and Delay in Anti-Tuberculous Treatment Are Important Risk Factors for Chronic Obstructive Pulmonary Disease. PLoS ONE 7(5): e37978.

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NCD Screening in TB Contact Tracing

Diabetes and TB Incidence

• Korea's National Health Insurance Data Analysis: Diabetic individuals exhibit a 48% increased risk of tuberculosis (TB).Risk escalates with diabetes duration; over 5 years of diabetes corresponds to a 57% heightened TB risk. Stronger diabetes-TB links observed in men and younger adults. Newly diagnosed diabetics with high fasting plasma glucose (FPG) levels face a 79% greater TB risk. See also: Lin TB Lab

TB Treatment Outcomes

• Study from Taiwan NHIRD (2002-2013): Post-TB treatment phases see elevated risks of diabetes, acute myocardial infarction (AMI), and stroke, especially with treatment durations of 7-12 months. Risks are influenced by age, gender, and pre-existing non-communicable diseases (NCDs).Emphasizes the need for vigilant monitoring for NCDs following TB treatment.

Latent TB in Type 1 Diabetes Patients

• Cross-Sectional Study in Dar es Salaam: 14.9% prevalence of latent TB among type 1 diabetes mellitus (T1DM) patients, with variations across developmental stages. Significant correlation found between uncontrolled HbA1c levels and higher latent TB prevalence.

Observational Challenges and Mendelian Randomization Insights

• Challenges in Diabetes and PTB Relationship Studies: Issues include reverse causality, confounding factors, and type differentiation (T1DM vs. T2DM).Poor glycemic control linked to increased TB risk; metabolic disturbances in T1DM enhance susceptibility to PTB.
• Mendelian Randomization Findings: Genetic studies suggest a link between T1DM and PTB, with correlations to higher HDL-C levels but no direct causal relationships with other T1DM-related traits.

TB and Non-Communicable Diseases in Myanmar

• Yangon, Myanmar Cross-Sectional Study: TB patients often exhibit behavioral risk factors like smoking and drinking more frequently than general population. Nutritional disparities show TB patients more likely to be underweight; significantly lower incidence of overweight/obesity. Higher diabetes prevalence among TB patients, with implications for integrated screening of NCDs during TB contact tracing.

Integration of NCD Screening in TB Contact Tracing

• Efficiency and Cost-Effectiveness: Incorporating NCD screening during TB contact investigations can identify undiagnosed conditions, improving early intervention and management. Highlights the necessity for community-wide screening initiatives, particularly for diabetes, to address the dual burden of TB and NCDs.

References:

1. Yoo JE, Kim D, Han K, Rhee SY, Shin DW, Lee H. Diabetes status and association with risk of tuberculosis among Korean adults. JAMA network open. 2021 Sep 1;4(9):e2126099.
2. Salindri, A.D., Wang, J.Y., Lin, H.H. and Magee, M.J., 2019. Post-tuberculosis incidence of diabetes, myocardial infarction, and stroke: retrospective cohort analysis of patients formerly treated for tuberculosis in Taiwan, 2002–2013. International Journal of Infectious Diseases, 84, pp.127-130.
3. Majaliwa, E.S., Muze, K., Godfrey, E., Byashalira, K., Mmbaga, B.T., Ramaiya, K. and Mfinanga, S.G., 2023. Latent tuberculosis in children and youth with type 1 diabetes mellitus in Dar es Salaam, Tanzania: a cross section survey. BMC Infectious Diseases, 23(1), p.740.
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. Zayar, N.N., Chotipanvithayakul, R., Bjertness, E., Htet, A.S., Geater, A.F. and Chongsuvivatwong, V., 2023. Vulnerability of NCDs and Mediating Effect of Risk Behaviors Among Tuberculosis Patients and Their Household Contacts Compared to the General Population in the Yangon Region, Myanmar. International Journal of General Medicine, pp.5909-5920.
6. Hamada, Y., Lugendo, A., Ntshiqa, T., Kubeka, G., Lalashowi, J.M., Mwastaula, S., Ntshamane, K., Sabi, I., Wilson, S., Copas, A. and Velen, K., 2024. A pilot cross-sectional study of non-communicable diseases in TB household contacts. IJTLD OPEN, 1(4), pp.154-159.

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Interaction between DM and TB exacerbates disease progression

Public Health Challenges and Epidemiology: Tuberculosis (TB) presents varying challenges across economic contexts. Rapid diagnosis and treatment are essential in regions with high TB prevalence to manage and prevent the disease, primarily through addressing the reactivation of latent TB infections (LTBI). In areas with lower incidence, TB tends to concentrate within high-risk groups, necessitating strategies tailored to local epidemiological patterns and social determinants. Additionally, understanding the demographic shifts towards older populations and the impact of diabetes mellitus (DM) on TB, including increased risk and poorer outcomes, is crucial.

Impact of Diabetes on Tuberculosis: Diabetes significantly increases the risk of developing active TB and affects treatment outcomes. The interaction between DM and TB exacerbates disease progression, with DM patients experiencing higher mycobacterial loads and unique lung lesions. This underscores the importance of integrated health strategies that simultaneously address both TB and DM, including enhanced screening and research into the transmission dynamics among these patients.

Study Insights and Special Populations:

• A study in metro Atlanta, Georgia (2016-2019) on HIV-negative adults with type 2 diabetes (T2DM) highlighted that LTBI was less prevalent in diabetic patients compared to controls. This suggests unique interplays between T2DM and LTBI, impacting screening and management approaches.
• The WHO emphasizes LTBI screening in populations with compromised immune systems, such as those undergoing dialysis or with chronic kidney disease (CKD), due to elevated TB risk.

Health Outcomes and Quality of Life in TB Survivors: TB survivors face considerable health challenges, including increased risks of TB recurrence and mortality. Chronic conditions such as respiratory diseases and cardiovascular issues are more prevalent among these individuals, leading to diminished quality of life and increased healthcare needs. Social and economic repercussions include stigma and financial hardship, emphasizing the need for comprehensive healthcare strategies that integrate TB care with broader health services to manage ongoing issues and improve life quality.

Epidemiological and Clinical Integration: The convergence of TB and DM epidemics, especially in regions like South-East Asia, the Western Pacific, and the Middle East, driven by rising rates of diabetes due to obesity and aging populations, calls for integrated public health responses. These should consider the compounded effects of both diseases on mortality, treatment failure, and relapse rates.

Advancements in Screening and Treatment: Advancements in technology and healthcare strategies, such as single-cell analysis and predictive modeling, hold promise for enhancing the understanding and management of TB-DM comorbidity. These tools can help in identifying new therapeutic targets and biomarkers, improving the precision of diagnostics and treatments.

Comprehensive Care for TB Survivors: Addressing the long-term health effects faced by TB survivors requires a multifaceted approach that includes lung function evaluations, pulmonary rehabilitation, and cardiovascular care. Economic support and social integration programs are also vital to mitigate the socio-economic impacts of TB on survivors and their families.

References:

1. Lee, P.H., Fu, H., Lee, M.R., Magee, M. and Lin, H.H., 2018. Tuberculosis and diabetes in low and moderate tuberculosis incidence countries. The International Journal of Tuberculosis and Lung Disease, 22(1), pp.7-16.
2. Salindri, A.D., Haw, J.S., Amere, G.A., Alese, J.T., Umpierrez, G.E. and Magee, M.J., 2021. Latent tuberculosis infection among patients with and without type-2 diabetes mellitus: results from a hospital case-control study in Atlanta. BMC Research Notes, 14(1), p.252.
3. Zhang, X., Chen, P. and Xu, G., 2022. Update of the mechanism and characteristics of tuberculosis in chronic kidney disease. Wiener klinische Wochenschrift, 134(13), pp.501-510.
4. Kaur, R., Egli, T., Paynter, J., Murphy, R., Perumal, L., Lee, A., Harrison, A., Christmas, T., Lewis, C. and Nisbet, M., 2023. Tuberculosis and diabetes: increased hospitalisations and mortality associated with renal impairment. Internal Medicine Journal, 53(9), pp.1588-1594.
5. Choi, H., Han, K., Jung, J.H., Park, S.H., Kim, S.H., Kang, H.K., Sohn, J.W., Shin, D.W. and Lee, H., 2023. Long-term mortality of tuberculosis survivors in Korea: a population-based longitudinal study. Clinical Infectious Diseases, 76(3), pp.e973-e981. See also: https://tbreadingnotes.blogspot.com/2024/07/non-communicable-diseases-in-tb.html
6. 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.

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Diabetes and Tuberculosis Interplay in Several Countries

Tuberculosis (TB) patients with diabetes mellitus (DM) are generally older, more often male, and exhibit higher rates of comorbidities such as hypertension and cardiovascular disease compared to non-diabetic TB patients. Despite these differences, there are no significant variations in symptoms, radiographic findings, or prevalence of acid-fast bacilli (AFB) positivity between controlled diabetics and non-diabetics. However, uncontrolled diabetic TB patients show higher rates of cavitary lesions and AFB positivity on sputum smears, reaching 65.8%, compared to 40.4% in non-diabetics. Poor glycemic control correlates with more severe disease manifestations, extended treatment durations, and increased risk of treatment failure and mortality.

The interaction between TB and DM is complex, with hyperglycemia impairing immune responses, including neutrophil function and adaptive immunity, thereby increasing susceptibility to TB. Uncontrolled diabetes quadruples the likelihood of TB diagnosis and exacerbates disease severity. The bidirectional relationship between TB and DM is evident as active TB can induce hyperglycemia, potentially leading to DM, while pre-existing DM worsens TB outcomes. Effective management of both conditions is critical to mitigating adverse effects, as improved TB treatment has been shown to normalize glucose levels in some cases.

A study at the Instituto Brasileiro para a Investigação da Tuberculose (IBIT) highlighted the significant association between glucose metabolism disorders (GMD) and TB. Among 892 participants, 63.1% exhibited elevated HbA1c levels, with 80% of pulmonary TB (PTB) cases showing abnormal glucose metabolism at diagnosis. Regression analyses confirmed that uncontrolled DM, especially in smokers, significantly increased TB risk. Poor glycemic control (HbA1c ≥7.0%) was a strong predictor of TB, and smokers with uncontrolled DM had an adjusted odds ratio of 6.3 for TB development.

Globally, TB remains a leading health challenge, with 10.4 million new cases and 1.7 million deaths reported in 2016, predominantly in low- and middle-income countries. DM, now a growing epidemic in these regions, compounds the burden, increasing the risk of TB incidence, treatment failure, and relapse. The interplay between TB and metabolic disorders extends beyond glucose metabolism, with TB-induced inflammation and epigenetic changes potentially increasing DM risk. Prospective studies are needed to clarify these mechanisms and guide interventions.

TB also poses long-term risks to respiratory and cardiovascular health. Post-TB complications such as cavitation, fibrosis, and bronchiectasis increase the risk of chronic lung diseases, including COPD, and cardiovascular events such as ischemic stroke. Distinguishing direct effects of TB from pre-existing risk factors is challenging but underscores the need for integrated care approaches.

A South Korean cohort study (2011–2018) further illustrated the compounded vulnerabilities of TB-DM patients, who were older, predominantly male, and had worse treatment outcomes, including higher mortality rates. TB was the leading cause of death in this group, while non-TB-related deaths were primarily due to lung cancer and pneumonia. Factors like advanced age, low income, and higher comorbidity scores were linked to poorer outcomes, emphasizing the need for targeted interventions.

A 2018 cross-sectional study in three geographic communities revealed disparities in pre-diabetes (PDM) and latent TB infection (LTBI). Urban areas had higher PDM prevalence, while rural settings had more LTBI cases. Logistic regression identified older age, smoking, lack of BCG vaccination, and abdominal obesity as significant predictors of PDM and LTBI. BCG vaccination notably reduced the risk of concurrent PDM-LTBI, underscoring its protective role.

Efforts to reduce TB-DM burdens must address the dual epidemic's challenges through integrated management strategies, large-scale clinical trials, and targeted interventions. Strengthening TB-DM care, especially in resource-limited settings, is essential to achieving global TB elimination goals.

See also: https://lintblab.weebly.com/research-topics.html

References:

1. Park, S.W., Shin, J.W., Kim, J.Y., Park, I.W., Choi, B.W., Choi, J.C. and Kim, Y.S., 2012. The effect of diabetic control status on the clinical features of pulmonary tuberculosis. European journal of clinical microbiology & infectious diseases, 31, pp.1305-1310.
2. Almeida-Junior JL, Gil-Santana L, Oliveira CAM, Castro S, Cafezeiro AS, Daltro C, et al. (2016) Glucose Metabolism Disorder Is Associated with Pulmonary Tuberculosis in Individuals with Respiratory Symptoms from Brazil. PLoS ONE 11(4):e0153590.
3. Zhao, L., Fan, K., Sun, X., Li, W., Qin, F., Shi, L., Gao, F. and Zheng, C., 2024. Host-directed therapy against mycobacterium tuberculosis infections with diabetes mellitus. Frontiers in Immunology, 14, p.1305325.
4. Magee, M.J., Salindri, A.D., Gujral, U.P., Auld, S.C., Bao, J., Haw, J.S., Lin, H.H. and Kornfeld, H., 2018. Convergence of non-communicable diseases and tuberculosis: a two-way street?. The International Journal of Tuberculosis and Lung Disease, 22(11), pp.1258-1268.
5. Bao, J., Hafner, R., Lin, Y., Lin, H.H. and Magee, M.J., 2018. Curbing the tuberculosis and diabetes co-epidemic: strategies for the integration of clinical care and research. The International Journal of Tuberculosis and Lung Disease, 22(10), pp.1111-1112.
6. Kwak SH, Jeong D, Mok J, Jeon D, Kang H-Y, Kim HJ, et al. (2023) Association between diabetes mellitus and cause of death in patients with tuberculosis: A Korean nationwide cohort study. PLoS ONE 18(12): e0295556.
7. Akinshipe, B.O., Yusuf, E.O., Akinshipe, F.O., Moronkeji, M.A. and Nwaobi, A.C., 2019. Prevalence and Determinants of Pre-diabetes and Latent Tuberculosis Infection Among Apparently Healthy Adults in Three Communities in Southern Nigeria. International Journal of Immunology, 7(2), pp.23-32.

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