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Dr. Michelle J. Alfa, FCCM Medical Director Microbiology, DSM Principal Investigator, SBRC

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Dr. Michelle J. Alfa, FCCM Medical Director Microbiology, DSM Principal Investigator, SBRC

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    2. Overview: Mycobacteria: Classification Pathogenesis of M.tuberculosis MTB disease Diagnosis of MTB Treatment of MTB Summary of Key Features

    3. Mycobacteria: Classification All are Acid fast bacilli (Kinyoun or Ziehl-Neelsen stain) - heat or phenol plus carbol fuschin - destain with acid-alcohol DO NOT stain by Gram stain - lipids, waxes are impermeable to stain unless heated or treated with phenol “Cording”: rope like formation of bacilli: - most common for M.tuberculosis

    4. Mycobacteria: Classification Nontuberculous Mycobacteria (NTM) - M. avium-intracellulae complex - M. kansasii - M. chelonae (rapid grower) Mycobacterium tuberculosis complex - M. tuberculosis - M. bovis - M. africanum - M. microti, - M. canettii, - M. pinnipedii

    5. Mycobacterium tuberculosis Aerobe Acid fast bacilli Mycolic acid, waxes & lipids in cell wall Slow growing (3 – 8 weeks to grow on agar) Risk Group 3 Forms “Infectious Droplet Nuclei”: remain airborne for long time

    6. Pathogenesis: M.tuberculosis Humans are the only reservoir Inhalation of droplet nuclei containing M.tuberculosis Replication in lungs (granuloma formation) Lymphohematogenous spread: dissemination throughout body inside macrophages Cell-mediate immune response leads to granuloma formation: Latent infection Reactivation

    7. Pathogenesis: M.tuberculosis Humans are the only reservoir Inhalation of droplet nuclei containing M.tuberculosis Replication in lungs (granuloma formation) Lymphohematogenous spread: dissemination throughout body inside macrophages Cell-mediate immune response leads to granuloma formation: Latent infection Reactivation

    8. Granuloma formation: Host Defense by “walling off” Granuloma formation: activated lymphocytes, macrophages, Langhans giant cells, fibroblasts and capillaries Caseous necrosis: ? leads to liquefaction of necrotic tissue leads to cavitation in lungs MTB in granuloma ? latent for years and then if immunity wanes the AFB can reactivate

    9. Granuloma: M.tuberculosis

    10. Key Virulence Factors of Mycobacteria tuberculosis Infectious droplet nuclei Resistant cell wall: - waxes, lipids, mycolic acid Intracellular survival Latency

    11. Survival within Macrophages

    12. Student Presentation: Role of Intracellular survival in Pathogenesis of M.tuberculosis

    13. Types of Infections: Acute infection: pneumonia [pulmonary TB] Latent chronic infection ? granuloma in lungs or any other site in the body Can manifest from any body organ or site so can present in many different ways

    14. Mycobacterium tuberculosis Pneumonia: Chest X-ray Infiltrates Nodules Calcified nodules

    15. Infection Control Issues: Respiratory TB 35% close contacts will get infected with TB Admitted: Airborne precautions (Air under negative pressure and is HEPA filtered before exhausted from room) Contact tracing: hospital and community Require 2 weeks of adequate therapy and 3 negative Respiratory samples (if original samples was AFB smear positive) before removal from Airborne precautions.

    16. Diagnostic Testing Culture is still the recommended method for diagnosing TB Detection of AFB in respiratory secretions Chest X-ray Tuberculin skin test (TST) Molecular diagnostic tests: not yet sensitive enough IGRA (Interferon gamma release assays): sensitized T-cells ? Latent TB detection

    17. Canadian Data: MTB cases

    18. Vaccine BCG vaccine (live M.bovis): protects from uncontrolled systemic spread ? up to 80% protection (ie. Doesn’t completely prevent risk of infection) Used in countries where endemic TB poses significant risk Canada: High risk groups ? Infants < 1 yr First Nations and Inuit communities (> 15 AFB smear positive pulmonary TB cases/100,000 pop)

    19. Extra-pulmonary TB Risk of transmission minimal Presentation can be confusing - testing may be delayed due to lack of suspicion about TB Most common sites: - GI tract - Liver - Brain - Genito-Urinary tract

    20. HIV: Risk of M.tuberculosis HIV patients at increased risk of TB - immunocompromised - First Nations HIV positive; drugs, crowded living conditions Harder to treat TB in HIV patients

    21. Drug resistant TB: More common in Foreign born Canadians TB drug resistance: resistant to one or more of first line drugs: isoniazid, rifampin, pyrazinamide and ethambutol (~ 5% in Canada) MDR-TB: resistance to at least INH and rifampin (~ 0.7% in Canada) XDR-TB: resistance to all first line therapeutic drugs (rare)

    22. Summary of Key Issues: M. tuberculosis: - Acid Fast Bacilli (AFB) - Risk group 3 bacterium - Humans are the only reservoir Pathogenesis: - Inhalation of infectious droplet nuclei - unrestricted replication ? spreads throughout body - Cell-mediated immune response - Granuloma formation ? latent infection - Reactivation if immunity wanes Public Health Risk - Pulmonary TB highest risk for spread - HIV link - MDR: multi-drug resistant strains

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