MYCOBACTERIA

1. MYCOBACTERIA MYCOBACTERIA Chapter 29

2. THE FOLLOWING SLIDE SHOW HAS BEEN RATED

3. Mycobacterium: Physiology & Structure • Name from Myces and Bakterion, Fungus-like Rod • Gram + • Bacillus • Aerobic • Nonmotile • Acid-Fast Staining • Mycolic Acid in Cell Wall • Complex Cell Wall • Intracellular Parasite • Diseases From Immune Response

4. Cell Wall • Complex • Contains Mycolic Acid • Lipids account for 60% of Cell Wall Weight • Responsible for Many Characteristics • Acid Fastness • Slow Growth • Resistance to Detergents • Antibiotic Resistance • Antigenicity • Clumping

5. The Cell Wall • Figure 29-1 Mycobacterial cell wall structure. The components include the (A) plasma membrane, (B) peptidoglycans, (C) arabinogalactan, (D) mannose-capped lipoarabinomannan, (E) plasma-associated and cell wall-associated proteins, (F) mycolic acids, and (G) glycolipid surface molecules associated with the mycolic acids. (Redrawn from Karakousis et al: Cell Microbiol 6:105-116, 2004.)

6. Really Important Mycobacteria

7. Mycobacterium tuberculosis

8. Pathogenesis & Immunity • Intracellular Pathogen • Lifelong Infection • Pulmonary Infection • Arrives at Alveoli • Phagocytized by Alveolar Macrophages • M.tuberculosis Blocks Phagosome From Fusing With lysosome (not nutrient containing vesicles, though) • Other Phagocytes Are Attracted • Forms Multinucleated Giant Cells (Langhans Cells)

9. Pathogenesis & Immunity • Infected Macrophages May Spread Infection • Stimulates TH Cells and TC Cells • Formation of Granulomas • Can Lead to Elimination of Bacteria • If Larger Than 3mm Become Encapsulated • M. tuberculosis can remain dormant for years in this state

10. Pathogenesis & Immunity

11. Epidemiology • 2 Billion People Infected World Wide • ONE-THIRD of the human population • 8.8 Million New Cases / Year • 2 Million Deaths / Year • 14,517 Cases in US in 2004 (11 in Idaho)

12. Mycobacterium leprae

13. Pathogenesis & Immunity • Causes Leprosy • Hansen’s Disease • Affects Skin and Peripheral Nerves Different Immune Responses Cause Different Forms • Tuberculoid • Lepromatous • Abundance of Bacteria in Two Types of Cells • Dermal Macrophages • Schwann Cells Figure 29-7 Lepromatous leprosy. Diffuse infiltration of the skin by multiple nodules of varying size, each with many bacteria. (From Cohen J, Powderly WB: Infectious diseases, ed 2, St Louis, 2004, Mosby.)

14. Pathogenesis & Immunity Table 29-2. Clinical and Immunologic Manifestations of Leprosy

15. Pathogenesis & Immunity Figure 29-6 Tuberculoid leprosy. Early tuberculoid lesions are characterized by anesthetic macules with hypopigmentation. (From Cohen J, Powderly WB: Infectious diseases, ed 2, St Louis, 2004, Mosby.)

16. Pathogenesis & Immunity • Figure 29-5 Acid-fast stains of skin biopsies from patients with (A) tuberculoid leprosy, (B) borderline tuberculoid leprosy, (C) borderline lepromatous leprosy, and (D) lepromatous leprosy. Note that there is a progressive increase in bacteria going from the tuberculoid form to the lepromatous form of the disease.

17. Epidemiology • 286,063 New Cases in Early 2005 • 21% Decrease Between 2004 and 2003 • ~20% Reduction in New Cases For The Last Three Years • Prevalence Has Fallen By 90% Since 1985 • 105 Cases in The US in 2004 • 16 countries -- Bangladesh, Brazil, Cambodia, Democratic Republic of the Congo, Ethiopia, Guinea, India, Indonesia, Madagascar, Mozambique, Myanmar, Nepal, Niger, Nigeria, Philippines, and Sudan -- reported more the 90% of the world's leprosy cases. • Listed By CDC In “CANDIDATE DISEASES FOR ELIMINATION OR ERADICATION” • Suseptability Gene found in 2003 by Canadian Team (http://www.cbc.ca/stories/2003/02/10/leprosy030210) Global distribution of leprosy, showing prevalence rates:       2.0–4.1 per 10,000 (9 countries)        1.0–2.0 per 10,000 (3 countries)        0.0–1.0 per 10,000 (data from only 73 countries)

18. Epidemiology • Endemic in Texas and Louisiana… In Armadillos

19. Lab Diagnosis • Box 29-5 • Detection • Acid-Fast Stain • Lung X-rays • Tuberculin skin test • Intradermal injection of mycobacterial antigens • Antigens used in skin test come from protein derivative of the cell wall • Inoculated into the intradermal layer • Measured 48 hours later • Positive test develops 3-4 weeks after exposure to M. tuberculosis

20. Table 29-3 for Results Skin test Induration~ Increase inflammation and marked by loss of elasticity and pliability Reaction is measured

21. Treatment, Prevention, & Control • Treatment • Slow growing and hard to treat (resistance) • Must be taken over long periods of time with multiple other antibiotics (6-9 months) • Regimens start with isoniazed (INH), ethambutol, pyrazinamide, and rifampin (2 months) • Followed with 4-6 months of INH, rifampin, and other combination drugs

22. Treatment, Prevention, & Control • Prevention • Treatment regimens are working and reducing the overall occurrence • Vaccinations are used in prevalent areas • (Can’t be used for immunocompromized patients) • Control • Elimination is highly unlikely, however, it can be controlled • Active surveillance and monitoring with therapeutic intervention • 44% decrease in (drug-resistant) tuberculosis in New York from 1991-1996