Mycobacterium tuberculosis

• Intracellular pathogen.
• Strategy to avoid digestion: resists the digestive components and prevents maturation of the phagolysosome.
• Acid fast, slow growing rods.
• Requires an acid fast stain.
• Grows on Lowenstein Jensen media.
• Cell wall is extremely hydrophobic (contributing to poor staining). Contains mannose capped lipoarabinomanan.
• Causes the disease Tuberculosis.
• Human spread.
• Colonizes alveolar macrophages, replicates in specialized vacuole.
• Active tuberculosis symptoms: chronic cough, fever, decreases appetite, weight loss, night sweats.
• Humans are the only natural reservoir.
• Primary Tuberculosis infection begins when contaminated respiratory droplets are inhaled. Outer mannose binds macrophage mannose receptors. Bacteria is engulfed by alveolar macrophages. Prevents phagosome maturation, establishing a replication vacuole. Eventually destroys the macrophage and infects more that are recruited. Eventually causes a solid granuloma to form, which prevents further spread.
• A macrophage that has not been 'activated' by a T-cell cannot digest M. tuberculosis.
• The center of a solid granuloma consists of a semi solid mass of necrotic cells and bacteria.
• Once a solid granuloma forms, there are two possible outcomes.

  If the bacterial burden is small when macrophages are activated, M. tuberculosis is destroyed with limited tissue damage.

  If there is a high bacterial burden, a large necrotic granuloma will form.
• A necrotic granuloma is encased by fibrin. The species cannot replicate inside due to low pH and anoxia but remains viable for years (latent tuberculosis).
• Secondary tuberculosis infection occurs when the patient immune system wanes. Wall of the necrotic granuloma becomes porous (creating a caseous granuloma), allowing bacteria to escape and infect macrophages again.
• Risk factors for tuberculosis: immune suppression (including HIV), nutrient starvation, hyperoxia.
• Primary infections last three to six weeks.
• Can disseminate to other tissues during an active infection.
• Lipoarabinomannan suppresses T-cell activation.
• Diagnosis:

  Latent or suspected:

  Mantoux test. INF gamma release test (will be elevated). Followed by a chest X-ray (will spot tubercles in latent disease).

  Active:

  Sputum used for an acid fast stain and culture on lowenstein jensen media. Nucleic acid amplification test. Chest x-ray.
• Active Treatment:

  For the first eight weeks: four antibiotics. Isoniazid, ethambutol, pyrazinamide, rifampicin.

  Then for twenty six weeks: isoniazid and rifampicin.
• Latent treatment:

  Isoniazid for thirty six weeks or isoniazid and rifapentine for twelve weeks.
• Live attenuated vaccine is called BCG.