Microbiology: All about Tuberculosis (TB)

Explore the global burden of tuberculosis, from historic epidemics and Koch’s discovery of Mycobacterium tuberculosis to current patterns of infection, latent disease, mortality, and regional hotspots.

Secondary tuberculosis represents reactivation of a prior latent tuberculosis infection, triggered when the immune system weakens. Most cases arise from reactivation, while about five percent result from reinfection.

Demystifies extrapulmonary tuberculosis, which can affect any organ beyond the lungs, accounts for 10–25% of TB infections, and is usually not infectious, especially in young children and people with HIV.

Explore how miliary TB arises from massive dissemination of Mycobacterium tuberculosis through the blood or lymphatic system, forming millet seed-sized granulomas in multiple organs.

Examine how HIV depletes CD4 T cells, elevating TB risk and severity, while TB accelerates HIV progression; both infections mutually worsen each other, making TB an opportunistic infection in HIV.

Malnutrition worsens tuberculosis by impairing immune responses and increasing energy needs, while TB promotes malnutrition through metabolic stress and nutrient losses, creating a vicious cycle.

Explore how tuberculosis during pregnancy raises risks for mother and fetus, including transmission, premature birth, and perinatal death, and how early treatment and micronutrient support improve outcomes.

Explore TB diagnosis with tests that emphasize sensitivity and specificity, using chest X-ray as the first step and follow-up sputum testing or CT to confirm and detail findings.

Learn how the Mantoux tuberculin skin test (PPD) uses delayed hypersensitivity and memory Th1 responses to detect TB exposure, with IFN-γ and TNF-α, measured by 48-72 hour induration.

Interferon gamma release assay (IGRA) detects Mycobacterium tuberculosis infection by measuring interferon gamma release after ESAT-6 and CFP-10 stimulation, offering higher specificity than TST and a single-visit result.

Stain sputum with Ziehl-Neelsen using carbol fuchsin and acid-alcohol to reveal red acid-fast bacilli, indicating possible TB within hours; culture is needed for confirmation and drug susceptibility.

A sputum culture detects TB bacteria and confirms active tuberculosis; it helps diagnose pulmonary and extra pulmonary TB using various specimens, though results take 4–6 weeks.

Discover first-line TB drugs (isoniazid, rifampicin, pyrazinamide, ethambutol) and the two-phase 6-month regimen for drug-susceptible pulmonary tuberculosis, including dosing and regimen notation like 2HREZ/4HR3.

First-line tuberculosis drugs disrupt cell wall synthesis and protein production. Isoniazid and ethambutol target mycolic acid and arabinogalactan synthesis; rifampicin blocks RNA polymerase; pyrazinamide acts in acidic environments.

Trace the history of tb drugs from world war ii to modern mdr-tb therapy, highlighting para-aminosalicylic acid, streptomycin, isoniazid, rifampin, pyrazinamide, ethambutol, and the 2012 emergence of delamanid and bedaquiline.

Improves detection of M. tuberculosis with higher sensitivity, including low-bacilli samples from HIV co-infected, pediatric, and extrapulmonary specimens, and enhances rifampicin resistance detection via a larger amplification chamber.

Learn how the line probe assay uses PCR and hybridization to rapidly detect rifampicin and isoniazid resistance in the Mycobacterium tuberculosis complex, through targeted rpoB, inhA, and katG probes.

Detect Mycobacterium tuberculosis and rifampicin resistance from sputum using TrueNat, a chip-based micro real-time PCR test, with automated DNA extraction and results in under an hour.

Rely on molecular tests for TB resistance only for known mutations (rpoB, inhA promoter, katG); use growth-based testing to monitor treatment progress and detect resistances beyond defined loci.

Explore group c and group d agents, including ethionamide or prothionamide, cycloserine or terizidone, linezolid, and clofazimine, in MDR-TB regimens.

Bedaquiline, a novel anti-tuberculosis drug for MDR-TB, blocks mycobacterial ATP synthase subunit c and must be used with other TB drugs under careful heart and liver monitoring.

Delamanid is a nitroimidazole anti-tuberculosis drug for multidrug-resistant tuberculosis, used with other medicines. It is a pro-drug activated by mycobacterial nitroreductase and inhibits mycolic acid synthesis.

The longer MDR-TB regimen prioritizes oral drugs from group A (bedaquiline, linezolid, and levofloxacin or moxifloxacin) and uses groups B and C to reach five effective medicines for 24 months.

The stream trial tests a 9–11 month all-oral regimen for MDR TB, showing non-inferiority to the 2011 WHO 20-month standard and comparing stage 2 oral bedaquiline against injectable kanamycin.

Investigate XDR-TB, an extensively drug-resistant TB, resistant to isoniazid, rifampicin, fluoroquinolones (levofloxacin, moxifloxacin), and at least one injectable second-line drug (amikacin, capreomycin, kanamycin), and how misuse and transmission drive resistance.

XDR-TB treatment requires a six-drug regimen over at least six months with injectables, followed by 12–18 months of therapy, guided by drug susceptibility testing, with costly drugs and serious side-effects.