Transcript Mycobacterium

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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
Cell Wall
• Complex
• Contains Mycolic Acid
– Lipids account for 60% of Cell
Wall Weight
• Responsible for Many
Characteristics
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–
–
–
–
–
Acid Fastness
Slow Growth
Resistance to Detergents
Antibiotic Resistance
Antigenicity
Clumping
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.)
Really Important Mycobacteria
Organism
Historical Derivation
M. tuberculosis
tuberculum, a small swelling or tubercle; osis, characterized by (characterized by tubercles;
refers to the formation of tubercles in the lungs of infected patients)
M. leprae
lepra, of leprosy (the cause of leprosy)
M. avium
avis, of birds (causes tuberculosis-like illness in birds)
M. intracellulare
intra, within, cella, small room (within cells; refers to the intracellular location of
mycobacteria)
BOX 29-1. Important Mycobacteria
Mycobacterium tuberculosis
Pathogenesis & Immunity
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•
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1.
2.
3.
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)
4. Other Phagocytes Are Attracted
5. Forms Multinucleated Giant Cells (Langhans Cells)
Pathogenesis & Immunity
• Infected Macrophages May Spread Infection
6. Stimulates TH Cells and TC Cells
7. 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
Pathogenesis & Immunity
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)
Mycobacterium leprae
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.)
Pathogenesis & Immunity
Features
Tuberculoid Leprosy
Lepromatous Leprosy
Skin lesions
Few erythematous or hypopigmented
plaques with flat centers and raised,
demarcated borders; peripheral nerve
damage with complete sensory loss;
visible enlargement of nerves
Many erythematous macules, papules, or
nodules; extensive tissue destruction (e.g.,
nasal cartilage, bones, ears); diffuse nerve
involvement with patchy sensory loss; lack of
nerve enlargement
Histopathology
Infiltration of lymphocytes around
center of of epithelial cells; presence
of Langhans cells; few or no acid-fast
rods observed
Predominantly "foamy" macrophages with
few lymphocytes; lack of Langhans cells;
numerous acid-fast rods in skin lesions and
internal organs
Infectivity
Low
High
Delayed
hypersensitivity
Reactivity to lepromin
Nonreactivity to lepromin
Immunoglobulin
levels
Normal
Hypergammaglobulinemia
Erythema
nodosum
Absent
Usually present
Immune response
Table 29-2. Clinical and Immunologic Manifestations of Leprosy
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.)
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.
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)
Epidemiology
• Endemic in Texas and
Louisiana…
In Armadillos
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
Table 29-3 for Results
Skin test
Induration~ Increase
inflammation and
marked by loss of
elasticity and pliability
Reaction is measured
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
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