Tuberculosis
Definitions
Mycobacterium tuberculosis
Granuloma - a small cluster of immune cells that forms to wall off something the body can’t easily eliminate
Infected - # of people who are infected\
TB - respiratory transmission, optimal conditions for transmission
Overcrowding
Poor personal hygiene
Poor public hygiene
Origins
Co-evolving with humans
Pathogenesis
Inhale droplet nuclei
Bacteria multiples
Macrophages consume bacteria, then die
Bloodstream
Transmission
Coughing
Sneezing
Shouting
Any way to expel bacilli into air
Spreads into
Lung
Renal cortex
Reticuloendothelial system
Mycobacterium
M. leprae and bovis
Slow growing
Thick cell wall
Macrophages
After engulfment, TB remains in the phagosome
Induces apoptosis in infected macrophages
Granuloma
Aggregation
Macrophages
T lymphocytes
B lymphocytes
Fibroblasts
Caseation - necrosis cell death
Virulence Mechanisms
Binds to mannose receptors on macrophages
Inhibits phagosome-lysosome fusion
TB interferes with toxic effects of oxygen
Slow gen time
Immune system not triggered quickly
Symptoms
Prolonged cough
Shortness of breath
Chest pain
Night sweats/fever/chills
Unexplained weight loss
Fatigue
PPD test
Precipitate of non-species-specific molecules obtained from filtrates of sterilized, concentrated cultures
Bacille Calmette-Guerin
Live attenuated strain
Administered at birth where TB is common
Classification of Drugs
First line - isoniazid, rifampin
Second line - p-amino salicylic acid, streptomycin, ethambutol
Third line - amikacin, kanamycin, capreomycin, viomycin, cycloserine
Multidrug-resistant - resistant to at least two of the best anti-TB drugs
Extensively drug resistant - resistant to more drugs
Isoniazid
Bacteriostatic for resting bacilli, stops bacteria from reproducing
Resistance
Failure of the drug to penetrate or be taken up by the microorganism
Rifampin
Resistance due to alteration of the target (DNA dependent RNA polymerase) of the drug, prevents further initiation but not elongation