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.

Tuberculosis spreads through the air when an infected person coughs or talks, releasing droplets that can be inhaled, with an infectious dose under 10 bacilli and no surface transmission.

Explore how inhaled Mycobacterium tuberculosis infects the lungs, survives in macrophages, forms caseous granulomas with epithelioid and Langhans giant cells, and yields latency via Ghon focus.

In about 5% of individuals, primary infection progresses to pulmonary or extrapulmonary TB due to high bacilli loads or weakened immunity, with granuloma rupture enabling dissemination.

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.

Explore latent TB infection and active TB, including how latent TB remains symptom-free and noninfectious, risk of progression if the immune system weakens, and symptoms and treatment of TB disease.

Explore risk factors that drive latent TB infection toward active disease, including close contact, HIV, organ transplantation, silicosis, smoking, underweight, diabetes, cancer, and immunosuppressive therapy.

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 the most common extrapulmonary TB forms—lymph node, pleural, urogenital, bone and joint, central nervous system, ocular, cutaneous, abdominal, and pericardial—with their symptoms.

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.

Identify risk factors for miliary TB, including HIV, alcoholism, malnutrition, chronic kidney disease, diabetes, cancer, pregnancy, and immunosuppressive therapy, and note organs like liver, spleen, bone marrow, lungs, kidneys, meninges.

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.

Explore immune reconstitution inflammatory syndrome (iris) in HIV patients starting antiretroviral therapy, where recovering immune cells unleash an exaggerated response to latent or dead tuberculosis bacteria, causing systemic inflammation.

Diabetes triples the risk of tuberculosis by impairing macrophage function and interferon gamma–mediated killing. The caption notes TB can also worsen glucose tolerance and rifampicin can affect glycemic control.

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.

Explain how MDR-TB resists isoniazid and rifampicin through mutations in katG, inhA promoter, ndhII, and rpoB; distinguish acquired and transmitted MDR-TB, and review global prevalence and treatment adherence factors.

Ensure MDR-TB prevention by taking all TB medications exactly as prescribed, completing therapy, and avoiding exposure in crowded health care settings through infection control and protective measures.

Identify drug resistance and guide effective MDR-TB treatment regimens through drug susceptibility testing, using phenotypic and molecular approaches for rapid or slower results.

Explain how the Xpert MTB/RIF assay uses real-time PCR in a cartridge to rapidly detect TB and rifampicin resistance in sputum via rpoB-targeting molecular beacon probes.

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.

Group A and B second-line drugs for MDR-TB include fluoroquinolones that inhibit DNA replication and aminoglycosides that misread codons, guiding the core MDR-TB regimen.

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.

Introduce the Bangladesh regimen, a nine-month shorter MDR-TB treatment for uncomplicated cases, featuring an initial kanamycin-based phase followed by a 5-month continuation, achieving high cure rates.

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.