Transcript M. Tuberculosis

Mycobacterium
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Incidence and prevalence
• One-third of the population worldwide is infected
• Every year
– 1.5 million people die from tuberculosis
– 8 to 10 million are newly infected.
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Main factors account for the resurgence of
tuberculosis in the United States
• Emergence of multidrug-resistant strains of M. tuberculosis
• Immigration of infected persons from countries where TB is
prevalent
• Prevalence of HIV infection and AIDS
• Reactivation of disease in the elderly
• Socioeconomic decline in urban areas
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Classification
Organisms
M. tuberculosis
complex
M. leprae
Growth rate
slow
Typical species
M. tuberculosis
M. bovis
No growth on
artificial media
Nontuberculosis
mycobacteria
Group Ⅰ
Slow
Group Ⅱ
Slow
M. Kansas 堪萨斯分枝杆菌
M. Marinum 海分枝杆菌
M. Scrofulaceum
Group Ⅲ
Slow
M. avium-intracellulare
Group Ⅳ
Rapid(<7d)
M. Fortuitum
瘰疬分枝杆菌
鸟－胞内分枝杆菌
偶发分支杆菌
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M. tuberculosis
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Biological properties
• Shape and structure
– Slender, rod-shaped bacterium, nonmotile
– Compositions
• peptidoglycan
• arabinogalactan layer
• high content lipid
– Mycolic acids
– Cord Factor
– Wax
•
polypeptide
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free lipids
(wax,cord
factor)
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Biological properties
• high content lipid
• Mycolic acids
• Cord Factor
• Wax
Acid-fast stain
Slow growth
Fastidious
A virulence factor
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Ziehl-Neelsen stain (acid-fast stain)
Acid-fast positive
• M.TB. smear, stained with
carbolfuchsin (15minutes)
• decolorized with acid-alcohol
• counterstained with
methylene-blue
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Biological properties
• Cultivation
obligate aerobes
slow growth: 18-24 hrs / 2-4 w
..
fastidious: Lowenstein-Jensen medium (L-J)
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Biological properties
• Sensitivity
moist heat
UV radiation
alcohol
• Resistance
dry
acid and alkaline
dyes: e.g., malachite green
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Pathogenicity
neither endotoxin or exotoxin nor invasive enzyme
intracellular pathogen
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•
Lipids
Protein
-- induces hypersensitivity of the host
Tuberculin test
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•
Polysaccharides
Mycobactin
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Lipid
•
Phospholipids
---proliferation of mononuclear cells, cause
tubercles
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Cord factor
---destroy mitochondria, suppress WBC
wandering ，cause chronic granulomatosis
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Wax D
---adjuvent, delayed-type hypersensitivity
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Sulfatide 硫酸脑苷脂
suppress phagosome combine with lysosome
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Pathogenicity
• Pathogens
M. tuberculosis-- only human host
M. bovis-- human and cattle
• Transmission
– respiratory route (main)
– gastrointestinal route
– impaired skin
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Pathogenicity
• Lung infection (pulmonary tuberculosis )
– Primary tuberculosis
– Post-primary (secondary) tuberculosis
• Extrapulmonary tuberculosis
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Pulmonary tuberculosis
• Primary tuberculosis
– Infected for the first time
– In young children
– Ghon complex (or primary
complex)
--combination of a single
lesion in lung and caseation
in regional lymph nodes in
the lung’s hilum
– Clinical type: usually mild and
asymptomatic
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Pulmonary tuberculosis
• Post-primary (secondary)
tuberculosis
– in the elderly or
immunosuppressed individuals
who have had primary infection
• the reactivation of the bacilli that
survived in the primary
tuberculosis
• the inhalation of new bacilli from
the environment
– clinical type: localized and severe
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Immunity
• Intracellular pathogen
• Immunological reaction
– Cell-mediated immunity (3 ～ 6 weeks after
infection)
– Humoral immunity: circulating Abs → no
defensive roles
– Infection immunity: The immunity to the bacilli
depends on the existence of organisms.
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Immunity
• Cell-mediated immunity & hypersensitivity
– develop at the same time mediated by T cells
– caused by different components of bacilli
– protein antigens (tuberculin along with wax D)
→ hypersensitivity
• Tuberculin test
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Tuberculin test
• Definition
a skin test to determine the presence of the
immunity and hypersensitivity of the host to M.
tuberculosis based on positive reaction of
subject to tuberculin
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Tuberculin test
• Materials
– old tuberculin (OT): heat-killed,
filtered proteins of M. Tuberculosis
– purified protein derivative (PPD)
• Methods
– intradermal infection of tuberculin
– read in 48-72 hrs
– Measure induration
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Tuberculin test
• Results and interpretation
– induration ≥ 5mm in diameter
---Positive
---Previous infection but not necessarily active
disease
---after BCG vaccination • early stage of infections
• the elderly
– induration ≥ 15mm in diameter
• patients with severe tuberculosis
---intensive positive
and other infectious disease (AIDS)
---active disease
• the use of immunosuppressive
drugs
– induration <5mm
--- a negative reaction
--- not contact with M. tuberculosis before
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---false reaction
Laboratory diagnosis
• Decontamination and concentration of specimens
– Treated with NaOH (sodium hydroxide) to kill other
contaminating bacteria
– Concentrated by centrifugation
• Smears— acid-fast stain
• Culture
– Use to confirm diagnosis of TB
• DNA detection, serology and antigen detection
– PCR (polymerase chain reaction)
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Prevention and Treatment
• Prevention
– BCG, bacillus Calmette-Guerin
• Made by Calmette and Guerin; since 1908
• heat-killed, filtered proteins of M.
Tuberculosis
• Recommended in immunization programs
or TB control programs in China
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Prevention and Treatment
• Treatment
– multiple drugs
– usually lasts for 6-9 months
– rifampin、isoniazid、streptomycin、prazinamide
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Nontuberculosis mycobacteria
Pigment
formation in:
Organisms
Growth rate Light Dark
Typical species
Slow
+
Group Ⅰ
M. Kansas 堪萨斯分枝杆菌
photochromogens
M. Marinum 海分枝杆菌
Group Ⅱ
scotochromogens
Slow
+
+
M. Scrofulaceum
Group Ⅲ
Nonchromogens
Slow
-
-
M. avium-intracellulare
Group Ⅳ
Rapid growers
Rapid(<7d)
瘰疬分枝杆菌
鸟－胞内分枝杆菌
M. Fortuitum
偶发分支杆菌
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Characteristics of nontuberculosis mycobacteria
• much less virulent than M. tuberculosis
• opportunistic pathogen in humans
• combined infection with M.tuberculosis, mostly
Mycobacterium avium-intracelluare complex.
very prominent cause of disease in AIDS patients.
• difficult to treat
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Mycobacterium leprae
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Biological properties
•
•
•
•
Intracellular parasites
Not grow on artificial media and cell culture
Grow in footpads of mice
Optimal temperature: 30℃
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4 forms of Leprosy
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•
•
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Lepromatous
Tuberculoid
Borderline
indeterminate
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Pathogenesis
• Transmission
Respiratory tract
Direct contact
• Disease-- leprosy (Hansen's Disease)
– Lepromatous type
– Tuberculoid type
– Infect skin, nerves
– Chronic disease
– Disfigurement
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Lepromatous type
Tuberculoid type
CMI
deficient
normal
lepromin
negative
positive
skin lesion abundant acid-fast
bacilli
course
progressive and
malign
infectivity high
few bacilli
benign and
nonprogressive
low
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