Lecture 13 Mycobacterium Tuberculosis Flashcards
Why does this TB bacteria presents humans with a challenge?
Due to its capacity to survive inside macrophages as a intracellular parasite and remain dormant for extremely long periods.
How many deaths are expected by TB?
1.2 million people die per year and antibiotic resistance is on the increase.
- Approx. 1 billion people will be infected between 2000-2020.
20-30 million will die of TB
What is the structure and physiology of TB?
- Weakly gram Positive + rod
- Acid fast staining**
- Aerobic
- Lipid rich cell wall-resistant to disinfectants, detergents, common antibiotics, and traditional strains.
- SLOW growing
What are the virulence factors for TB
- No capsule
- No Toxin (LPS)
- Lipid coat is essentially THE VIRULENCE FACTOR
Epidemiology:
How many are infected and who is affected?
- 2 billion infected
- 1,000,000 deaths each year
- impoverished countries mainly affected
- Humans only resevior
Who is at greater risk of TB?
- Immunocompromised
- in crowded conditions:
- Can spread disease
- HIV
- Tumors
- Drug/ alcohol abusers
- Homeless
- Poor nutrition
- Immune therapy
- prisons
Characteristics of TB?
- ***In most individuals latent TB infections is established
- Majority of TB cases are \pulmonary
- Dissemination to any body sure occurs most commonly in immunocompromised patients.
- Disease caused primarily from the host response to infection
Diagnosis– signs /symptoms
Cough (duration > 3 weeks)
Chest pain
-Fever& Night Sweats
Coughing up blood or bloody sputum
Positive + TB skin test (Mantoux tuberculin test)
-QuantiFERON-TB test
-chest radiograph
-Microscopy and culture are sensitive and specific
-PCR is getting cheaper and better, very fast (e.g Xpert MTB/RIF)
Tx, prevention and control established?
***The only way to eliminate TV is with long-term multi-drug, anti-microbial and antibiotic therapy !
6-9 mo minimum
2-6 mo prophylaxis after exposure
Directly observe therapy (DOT) or DOTS becoming the norm
Immunization with BCG (attenuated strain of M. bovis)
Immunization with BCG of individuals with high risk in the US (not HIV+)
Mycobacterium Bacteria morphology and physiology ?
- curved rods
- acid fast
- high lipid = 60 % dry weight
- Non motile
- No spores
- No toxin
- No capsule
- Obligate aerobe –> likes lung
- resistant to chemicals and drying
- Heat sensitive –>milk pasteurization
What is the other imporant Mycobacterium species?
M. leprae that causes Leprosy
What is acid-fast staining?
unique to Mycobacterium and the cells remain stained even after an extended acid-alcohol wash and is very aerobic.
What is the major virulent factor?
The lipid-rich cell wall that helps allow it to be resistant to macrophage killing
What are the issues with Tx
Complacency, poor compliance and multi-drug resistance
How is M. Tuberculosus successful?
It is able to avoid destruction from macrophages! Virulence factors include waxy lipid coat and mycolic acids :)
-Tis allows the M. tuberculosis to escape death in the phagolysosome of macrophages. So–> it replicates with the macrophage cytoplasm unharmed.
What is the primary detection method?
- *TB detected by clincal presentation or PPD TB skin test (tuberculin skin test).
- X-rays and identification thru culture of the bacteria from sputum samples confirm diagnosis.
What causes TB to resist drug access?
Slow growing M. tuberculosis is usually held within a granuloma that redistricts drug access.
BCG vaccine ?
used most of the world (exception of the US) and is about 80% effective at preventing disease ( The PPD skin test useless)
What are the MHC like molecules that are used with TB?
CD 1 are able to present the lipids of M. tuberculosis to certain T cells (mostly NK T cells)
*Another MHC related molecule is MR1 which is able to present molecules derived from B vitamins such as folic acid to mucosal-associated invariant T (MAIT) cells.