MTB

• Every year, ten million people fall ill with tuberculosis, or so-called TB, despite being a preventable and curable disease
• 1.5 million people die from TB each year, making it the world's stop infectious killer
• TB is the leading cause of death of people with HIV, and also a major contributor to antimicrobial resistance
• Most of the people who fall in with TB live in low and middle income countries, but TB is present all over the world; about of all people with TB can be found in eight countries such as Bangladesh, China, India, Indonesia, Nigeria, Pakistan, Philippines, and South Africa
• About one quarter of the world's population is estimated to be infected by TB bacteria. Only 5 – 15% of these people will fall ill with active TB disease, so the rest of TB infection are not ill and cannot transmit the disease
• Both TB infection and disease are curable using antibiotics
• Mycobacteria


  • Aerobic, although some may grow in reduced oxygen concentrations
  • Non-spore-forming EXCEPT for Mycobacterium marinum
  • Non-motile, slightly curved or straight rods
  • Usually, 0.2 – 0.6, or 1 – 10 mm in size
  • Some species may display a branching morphology
• Mycobacterium


  The only genus in the Mycobacteriaceae family, under the order Actinomycetales, in the Actinomycetes class
• Genera closely related to Mycobacterium

  • Nocardia
  • Rhodococcus
  • Tsukamurella
  • Gordonia

  
• Mycobacterium cell wall

  • Contains N-glycolyneuraminic acid instead of N-acetylmuramic acid
  • Has a very high lipid content (Mycolic acid) which creates a hydrophobic permeability barrier
  • Difficult to stain with commonly used basic aniline dyes such as those used in Gram staining
  • Generally considered Gram-positive
  • Resist decolorization with acidified alcohol or 3% hydrochloric acid after prolonged application of a basic fuchsin dye, or with heating of this dye after its application
• Acid-fastness

  Important property of mycobacteria derived from their cell wall structure, which distinguishes them from other genera
• Key features of mycobacteria

  • Cell wall has extremely high lipid (Mycolic Acid) content
  • Resist decolorization with acid-alcohol
  • Acid-fast bacilli (AFB): basic distinguishing feature
  • Most pathogenic species require 2 – 6 weeks of incubation
  • Most are slow growers EXCEPT M. fortuitum-chelonei: grows in at least 3 days on Modified MaC
  • M. leprae – fails to grow in vitro (using agarose medium)
• Mycobacterium tuberculosis


  • Also known as Koch's bacillus/ Tubercle Bacilli
  • Agent of Tuberculosis
  • A chronic infection (host carry the organism chronically)
  • 20th century – 2nd leading cause of death
• The bacteria usually attack the lungs, but it can attack any part of the body such as the kidney, spine, and brain
• Latent TB Infection (LTBI)


  One of the two TB-related infections, where not everyone infected with TB bacteria becomes sick
• TB Disease


  One of the two TB-related infections, where if not treated properly, can be fatal
• Mycobacterium tuberculosis virulence factors

  • Mycoside – mycolic acid bound to a carbohydrate
  • Cord Factor - A mycoside formed by the union of two mycolic acid with a disaccharide (trehalose), inhibits neutrophil migration and damages mitochondria, releases tumor necrosis factor resulting in rapid weight loss
  • Sulfatides - Are mycosides that resemble cord factor with sulfates attached to the disaccharide, inhibit the phagosome from fusing with the lysosome that contain bacteriocidal enzymes
  • Wax D - Is a complicated mycoside that acts as an adjuvant (enhances antibody formation to an antigen) and activates the protective cellular immune system
• Tuberculosis


  • A disease of the respiratory tract (pulmonary TB, or PTB)
  • Acquired by person with active disease by means of cough, sneezing or talking
• TB bacteria spread through the air from person to person by inhalation of droplet nuclei containing the organism
• Infectious aerosols, usually 1 – 5 um in size are produced when people with pulmonary tuberculosis couch, sneeze, speak, or sing
• Infectious aerosols may also be produced by manipulation of lesions, or processing of clinical specimens in the laboratory
• Once inhaled, the bacteria can settle in the lungs and begin to grow, and from there they can move through the blood and to other parts of the body, such as the kidney, spine, or brain
• TB disease in the lungs or throat can be infectious, but TB in other parts of the body such as the kidney or spine are usually not infectious
• Chest radiograph is useful for the diagnosis of TB disease, as chest abnormalities can suggest pulmonary TB disease

  
• In pulmonary TB disease, radiographic abnormalities are often seen in the apical and posterior segments of the upper lobe or in the superior segments of the lower lobe, but lesions may appear anywhere in the lungs and may differ in size, shape, density, and cavitation
• Radiographic abnormalities in children tend to be minimal with a greater likelihood of lymphadenopathy, more easily diagnosed on the lateral film; mixed nodular and fibrotic lesions may contain slowly multiplying tubercle bacilli, and have the potential for progression to TB disease
• Primary Tuberculosis: Pathogenesis

  1. M. tuberculosis cells are phagocytized by alveolar macrophages and are capable of intracellular multiplication

  2. In a person with adequate cellular immunity, T cells arrive within 4 – 6 weeks owing to macrophage-activating polypeptides termed lymphokines

  3. This enables the macrophage in the area of infection to destroy the intracellular mycobacteria

  4. There is then a regression and healing of the primary lesion, and any disseminated foci of … (putol)

  5. Granuloma, or a hard tubercle, form in the lung. From the lymphocyte to the macrophages in cellular pathology including giant cell formation or cellular fusions displaying multiple nuclei
• If the mycobacterium antigen concentration is high, a hypersensitivity reaction may result in tissue necrosis caused by enzymes released from the macrophages. In this case, no granuloma forms, and a solid or semi-solid caseous material is left at the primary lesion sites
• In patients infected with primary active tuberculosis, the disease may spread via the lymph system, or hematogenously, leading to meningeal or miliary or disseminated tuberculosis. This often occurs in patients with depressed or ineffective cellular immunity
• In many exposed individuals, the immune system does not eliminate the bacteria
• If there is little antigen and a strong hypersensitivity reaction, a hard tubercle or granuloma may be formed - an organization of lymphocytes, macrophages, fibroblasts, and capillaries
• With granuloma formation, healing occurs, as well as fibrosis, encapsulation, and calcification, with scar formation as a reminder of the past infection
• Pott's disease


  Tuberculosis Spondylitis or Skeletal TB of the Spine, involving invasion into the spinal vertebrae, can cause bone destruction, deformity, and paraplegia
• Miliary Tuberculosis


  Seeding of many organs outside the pulmonary tree (Extrapulmonary tuberculosis), common sites include spleen, liver, lungs, BM, kidney, adrenal gland, and eyes
• Miliary tuberculosis is a potentially fatal form of the disseminated disease due to the hematogenous spread of tubercle bacilli to the lungs and other organs, resulting in the formation of millet seed size, usually 1 – 2 mm in size, of a tuberculous foci
• Latent TB Infection (LTBI)


  One of the two TB-related infections, where the infection can be treated, and without treatment, can progress to TB disease
• TB Disease


  One of the two TB-related infections, which is curable by a standard six-month course of four antibiotics (first-line TB drugs: Rifampicin, Isoniazid, Pyrazinamide, Ethambutol, Streptomycin)
• Second-line TB drugs


  • Ethionamide
  • Capreomycin
  • Ciprofloxacin
  • Cycloserine
  • Rifabutin
  • Ofloxacin
  • Kanamycin
• In some cases, the TB bacteria can develop drug resistance, requiring the use of second-line TB drugs
• Disseminated disease

  Due to the hematogenous spread of tubercle bacilli to the lungs and other organs, resulting in the formation of millet seed size, usually 1 – 2 mm in size, of a tuberculous foci