Mycobacterium

Question 1

Mycobacterium (General)

Answer 1

• Pulmonary:
• M. Tuberculosis-Human pathogen
• M. Bovis-Animals, transmitted via milk w/TB like symptoms
• Pulm Atypical:
• M. Avium complex-TB like, affects HIV pts
• M. Kansasi-TB like, affects HIV pts
• Skin manifestations:
• M. Laprae-Leprosy & human pathogen
• M. Marinum-Skin granulomas, in water (swimming pool/fish tank)
• M. ulcerans-Skin infection=Buruli ulcer (tropical)

Question 2

Mycobacterium Tuberculosis (general)

Answer 2

• Acid fast, Rod, obligate aerobic (non-spore)
• Facultative intracellular ^{<em><strong>(inside phago cells)</strong></em>}
• High in guanine/cytosine ratio (like gram +)
• Difference from gram + is RICH in complex lipids = Long chain FAs w/70-90 carbons
• DO not gram stain (thick lipids)
• Slower grower (24 hours)
• Production of NIACIN differs TB from other mycobacterium
• Cell wall:
• 50% mycolic acid w/a peptidoglycan layer made of D-arabinose/D-galactose
• Resistance to antibiotics & acidic/alkaline compounds
  
  • _{<strong>^{Allows for survival inside macrophages}</strong>}
• Cord factor=Trehalose dimycolate
• Lipid comp-responsible for parallel clumping (serpent appearance)-W/o this factor Can NOT grow in phago cell

Question 3

Mycobacterium Tuberculosis (Pathogenesis)

Answer 3

• Transmission: Human to Human-Can survive for 8 months in air
• High risk: Malnutrition, crowded conditions, drug users
• 1/3 of world’s pop infected & HIV increased prevalence of TB
• NO cap, exotoxin or endotoxin
• Create FUSION of phagosome/lysosomes=Prevention of oxidative killing
• Lungs primary target-1st exposure pts has no specific immunity
• Infected macrophages secrete IL-12 & TNF-a=Inflammatory response
• Macrophages–>T lymph–>TH to TH1
• TH1 secretes INGy–>macrophage kill bacteria

Question 4

Mycobacterium Tuberculosis (Spread)

Answer 4

• Progression depends on host’s infectious dose & immune competence
• Granulomatous lesions: Epitheloid cells, giant cells, T-lymphocytes
• Central caseous necrosis bacteria can remain here for long time
• Tubercle: granuloma surrounded by fibrous tissue
• Ghon complex: made as macrophage carries organism to lymph=forming granuloma (Lung)
• Some cases NO disease infection arrested in granuloma

Question 5

Mycobacterium Tuberculosis (Diseases)

Answer 5

1. Primary TB: Bacterial replication NOT arrested=Cavitary lung disease, cough, sputum, fever, night sweats (lower lung)
2. Latent TB: NO clinical symptoms-bacteria alive in granuloma
3. Reactivation TB-Appears in Upper lung due to impairment of immunity

• Tubercle lesion rupture=Cavity created bacteria can spread leading to Miliary
  1. Miliary(Multiple foci): Disseminated=Extrapulmonary
• In joints = Pott’s syndrome

Question 6

Mycobacterium Tuberculosis (Diagnosis)

Answer 6

• Tuberculin/Mantoux/PPD test: Hypersensitivity test to TB proteins
• X-ray: used in conjunction w/PPD
  
  • looking for tubercles, ghon-complexes, cavities
• Staining/microscopy: Acid fast staining/Ziehl-Neelsen
• Requires heating of stain, decolorize w/acid-alcohol sol, seconday dye
  
  • Found in sputum
  • Fluorochrome stain w/Auramin-rhodamine (appears yellow)
• Interferon-gamma assays: Measures how immune system reacts to bacteria w/TB
• Culture: Middlebrook 7H10/Lowenstein Jensen = egg media use ofNa+hydroxide for contaminants ^{(2 to 8 weeks)}

Question 7

Tuberculling/Mantoux/PPD test

Answer 7

• Detects past, latent or current infection
• Measure diameter of hard swelling
• Depends on 3 categories:

1. 5 mm or more=(+): HIV pts, recent contact of TB or pts w/abnormal CXR
2. 10 mm or more=(+): Recent migrants, residents of crowded areas, health care workers, Immunocompromised
3. 15 mm or more=(+): People w/no known risk factor

• PPD + pts use of IGRAs to comfirm diagnosis
• Measure amount of IFN-y due to TB activation of T-cells = *INCREASE *

Question 8

Mycobacterium Tuberculosis (Treatment)

Answer 8

• Multi-drugs for several months (6-9)
• Rifampin (RIF):
  
  • _{^{inhibit DNA dependent RNA polymerase}}
• Interfere with mycolic acid synthesis:
• Isoniazid (INH)
• Pyrazinamide (PZA)
• Ethambutol (EMB)
• Resistant strains/develop from treatment misuse/mismanagement:
• MDR-TB=Multi drug resistant (INH/RIF)
• XDR-TB=EXTREME drug resistant
• MDR/quinolone/Aminoglycoside
• BCG vaccine (Bacille calmette-Guerin)=Attenuate bovine strain given to children & military