Tuberculosis 101

Tuberculosis (TB) is an airborne disease transmitted by inhaling droplet nuclei, ranging from 1 to 5 µm, released when contagious individuals cough, speak, sing, or sneeze. After exposure to Mycobacterium tuberculosis (Mtb), around 20–25% of individuals become infected. Of these, 5–10% may develop active TB within the first five years. In the remaining 90%, the immune system—via innate and adaptive responses—controls the pathogen's replication. About 10% of infected individuals may develop active TB at some point in their lifetime. The risk is significantly higher for those co-infected with HIV, with a 10% annual risk and up to a 50% lifetime risk of developing active TB. The term "latent tuberculosis infection" (LTBI) refers to a state of persistent immune response to Mtb antigens, as detected by tests like the tuberculin skin test (TST) or interferon-gamma (IFN-γ) release assay (IGRA), without clinical signs of active TB. Historically, a dualistic approach—classifying ...

Hyperglycemia impairs the immune system, reducing the body's ability to respond effectively to Mycobacterium tuberculosis (M. tuberculosis). This weakened response can lead to delayed bacterial clearance, prolonged infectivity, and an increased risk of TB relapse. Hyperglycemia also disrupts the balance between pro-inflammatory and anti-inflammatory cytokines, creating an unfavorable immune environment for TB control. Recognizing the impact of hyperglycemia on TB treatment outcomes is essential for improving patient care and developing effective management strategies. In our cohort study of 791 patients with pulmonary TB (PTB) in Shandong Province, China, 33.6% (266 patients) exhibited hyperglycemia. While smoking and drinking habits were similar between hyperglycemic and non-hyperglycemic groups, patients with hyperglycemia were predominantly older, male, married, rural residents, and had lower educational levels and a higher BMI. Hyperglycemic patients also had more extensive lu...

Compared to the 9H regimen, the 3-month weekly rifapentine plus isoniazid (3HP) regimen has similar efficacy in TB prevention, a lower risk of hepatotoxicity, a 10% higher completion rate, and greater cost-effectiveness. In this pilot project, funded by the Taiwan CDC, patients with pre-diabetes mellitus (pDM) were enrolled by endocrinologists and treated by pulmonologists as part of a multidisciplinary team in two hospitals. We reported the screening and preventive therapy completion rates for LTBI, with a focus on the 3HP regimen. This prospective study was conducted between April 2018 and June 2020 at a medical center in Taichung and a regional hospital in Kaohsiung. Through collaboration among public health professionals, endocrinologists, and pulmonologists, programmatic LTBI intervention achieved a 92.7% LTBI screening rate and an 82.5% completion rate among patients receiving TPT. Approximately one-quarter of patients with pDM had LTBI, a prevalence higher than that of TB close ...

Mendelian randomization (MR) is a scientific approach used to assess causal relationships between modifiable risk factors and clinically relevant outcomes by utilizing genetic variants as instrumental variables in natural experiments. This method, which relies on genome-wide association studies (GWAS) data, provides valuable insights into potential causal connections, enabling researchers to make informed decisions regarding preventive measures and therapeutic interventions. Randomized controlled trials (RCTs) remain the gold standard for establishing causality. However, when clinical research is too costly, impractical, or unethical, MR has become a compelling alternative. Compared to traditional observational studies, MR is less susceptible to confounding factors and reverse causality since it focuses on genetic components rather than environmental ones. In this study, the causal relationships between metabolic factors and pulmonary tuberculosis (PTB) were examined through two-sample...

A triage test with a minimum sensitivity of 90% and specificity of 70%, meeting predefined operational targets, could help reduce underdiagnosis and misdiagnosis of tuberculosis, decrease delays in starting treatment, and lower the cost and infrastructure demands of current gold-standard sputum-based tests in high-burden settings.  Sweeney and colleagues validated a three-gene host blood signature, utilizing blood mRNA to measure markers associated with the host inflammatory response, which can differentiate tuberculosis disease from other conditions. This signature has been developed into an automated, blood-based quantitative PCR test on the GeneXpert platform, generating a TB Score based on the cycle threshold of expressed genes. Early studies from stored samples and interim results from a multisite study suggest that this test may achieve the WHO's target product profile minimum accuracy threshold for a tuberculosis triage test. We aimed to prospectively evaluate the diagnostic...

Risk factors for tuberculosis (TB) fall into two main categories: those recently infected with TB and those with an immunocompromised status. The latter includes individuals with HIV, diabetes mellitus (DM), transplant recipients, malnourished individuals, tobacco users, and those receiving immunosuppressive treatments. It was estimated that 629 million people expected to be impacted by DM by 2045. Diabetes increases the risk of TB incidence by 2-4 times and is associated with poorer treatment outcomes, doubling the risk of mortality during TB treatment. Long-term hyperglycemia and poor glycemic control (PGC) impair immunity, leading to increased susceptibility to TB. In contrast, optimal glycemic control (OGC) has been shown to improve TB outcomes by enhancing phagocytic activity and other immunological defenses. Patients with OGC exhibit a reduced risk of adverse treatment outcomes, lower sputum positivity rates, and a decreased risk of cavitary lesions on radiologic examinations com...