TB TW ID etc.: The Role of Smoking, Diabetes, and New Diagnostic Tools

Current smoking is linked to a twofold increase in active TB risk compared to never-smokers, with risk increasing based on the number of cigarettes, years of smoking, and pack-years.
Smoking accounts for 17% of TB cases in the studied population, emphasizing its role in TB incidence.
Current smokers have a higher TB risk than former smokers, indicating reduced hazard among those who quit.
The smoking-related TB risk is higher in individuals under 65, potentially due to early depletion of susceptible populations among older smokers.
Smoking weakens key pulmonary defense mechanisms, making individuals more susceptible to TB upon exposure.

Low Case Identification and Diagnosis: Only about a third of estimated DR-TB cases were identified and reported, with just a tenth of true cases diagnosed.
Inadequate Diagnostic Support: Approximately half of the treatment regimens were backed by phenotypic drug susceptibility testing (pDST).
High Unsuccessful Treatment Outcomes: Nearly half of patients initiating treatment had unsuccessful outcomes.
Significant Delays in Treatment: Notable delays between diagnosis and treatment, especially for those living further away, employed individuals, and those with private sector engagement.
Impact of Undetected DR-TB: Undetected DR-TB contributes to ongoing transmission, complicating global efforts to eliminate TB. Increased testing and treatment may strain health systems.
Potential of Active Case Finding: Active case finding is cost-effective when integrated into a national TB program, aiding in the detection of DR-TB, especially new cases.
Challenges in Urban Settings: In urban areas of Indonesia, delays and losses in DR-TB case finding, pDST testing, and treatment outcomes are prevalent. Improving diagnostic access and patient care linkages could reduce transmission.

Accelerated Decline in TB Burden: A new diagnostic tool is expected to reduce pulmonary TB burden more rapidly than reliance on smear microscopy.
Influence of Contextual Factors: The tool's impact on TB epidemiology is significantly affected by non-performance-related contextual factors.
Greatest Impact in Certain Settings: The tool has the most impact in areas with good access to care but low-sensitivity diagnostic strategies.
Lesser Impact in Equipped Laboratories: The tool's population-level impact may be reduced in reference labs with existing sensitive diagnostic tools, like cultures.
Increased Patient Trust: A new diagnostic test can enhance patient trust in the healthcare system, potentially reducing delays in TB diagnosis.
Reduced Diagnostic Default: Quick turnaround times may decrease the need for multiple healthcare visits, lowering patient default rates.

Mono-resistant TB: Resistance to one first-line anti-TB drug only.
Isoniazid-resistant TB: Resistance to Isoniazid, but susceptibility to Rifampicin.
Poly-resistant TB: Resistance to more than one first-line anti-TB drug, excluding both Isoniazid and Rifampicin.
Rifampicin-resistant TB (RR): Resistance to Rifampicin, with or without resistance to other anti-TB drugs.
Multidrug-resistant TB (MDR-TB): Resistance to at least both Isoniazid and Rifampicin.
Pre-extensively drug-resistant TB: Resistance to Rifampicin, Isoniazid, and either Fluoroquinolones or one injectable drug.
Extensively drug-resistant TB (XDR-TB): Resistance to any fluoroquinolone and at least one second-line injectable drug, in addition to MDR.

Rifampicin: Inhibits RNA synthesis by binding to RNA polymerase; side effects include hepatotoxicity, immunological reactions, and renal failure.
Isoniazid: Inhibits mycolic acid synthesis in mycobacterial cell walls; side effects include neuropathy and hematological disorders.
Ethambutol: Inhibits mycobacterial cell wall synthesis; causes bacterial aggregation and morphological changes.
Pyrazinamide: Inhibits fatty acid synthesis in MTB, activated under acidic conditions.

Phenotypic Testing: Culture-based method with high sensitivity; results in 2-3 months.
Genotypic Testing: Molecular tests identify resistance mutations; faster than phenotypic testing.
GeneXpert: A NAAT test detecting TB and Rifampicin resistance within 2 hours.

Pathophysiological Mechanisms: DM patients show diminished cellular immunity, impaired macrophage function, and reduced interferon gamma levels, increasing TB risk.
Bidirectional Relationship: TB and DM often coexist, presenting a dual health challenge, especially in low and middle-income countries.
Increased TB Risk in DM Patients: DM patients have a higher prevalence of active TB, which exacerbates the overall TB burden.

Sources:

Lin, H.H., Ezzati, M., Chang, H.Y. and Murray, M., 2009. Association between tobacco smoking and active tuberculosis in Taiwan: prospective cohort study. American journal of respiratory and critical care medicine, 180(5), pp.475-480.
Lestari, B.W., Nijman, G., Larasmanah, A., Soeroto, A.Y., Santoso, P., Alisjahbana, B., Chaidir, L., Andriyoko, B., Van Crevel, R. and Hill, P.C., 2024. Management of drug-resistant tuberculosis in Indonesia: a four-year cascade of care analysis. The Lancet Regional Health-Southeast Asia, 22:100294.
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.
Wulandari, D.A., Hartati, Y.W., Ibrahim, A.U. and Pitaloka, D.A.E., 2024. Multidrug-resistant tuberculosis. Clinica Chimica Acta, 559, p.119701.
Tariq, M., Zafar, S., Waheed, A., Afzal, N., Razzaq, R. and Batool, F., 2023. Prevalence of Various Forms of Active Tuberculosis in Patients with Diabetes. THE THERAPIST (Journal of Therapies & Rehabilitation Sciences), pp.33-37.

TB TW ID etc.