Mycobacterial Diseases I & II Flashcards
1
Q
Unique properties of mycobacteria
A
- Slow-growing: 3-6 weeks for isolation
- 60% of their cell wall is lipid, largely composed of mycolic acids
- Very difficult to gram stain
- Resist de-staining once stained = acid-fast
- Resistant to dessication –> viable after 6-8 months in dried sputum
- Resistant to many disinfectants, but you can kill them with UV light
2
Q
Transmission of M. tuberculosis & odds of developing disease
A
- Respiratory droplets from active infection via cough, sneeze, or speaking
- Only need 1 bug to catch it
- 5% w/ infected contacts will progress from positive PPD to active TB within first 2 years
- 5% chance will develop active TB in their lifetime beyond that 2 years
- HIV-infected person with latent TB have a 7-10% chance of developing active TB each year
- Other conditions (diabetes, ESRD, immunosuppression) also have increased chance of developing active TB
3
Q
Development of immunity to M. tuberculosis
A
- Initial infection: no symptoms or mild flu-like disease
-
Cell-mediated immunity develops at 2-6 weeks, dominated by Th1s
- Control of infection is via cell-mediate immunity
- Abs do not play a major role in recovery or prevention
- Antigen-specific CD4+ Th cells secrete IFN-gamma which attracts/activates macrophages
- Macrophages kill intracellular bacteria (TB) or at least slow growth
4
Q
Immune factors known to control M. tuberculosis
A
- **IFN-gamma **and TNF-a (released by macrophages)
- If inhibited with drugs for other conditions, you risk reactivation of latent infection
- When macrophages die, bacilli released - travel through lymph to bloodstream and can get to rest of body –> liver, spleen, kidney, bone, brain, meninges, and lung again
- Granulomas:
- Site of confined bacteria
- Made up of epithelioid cells, giant cells, and lymphocytes
- Centers become necrotic as they grow (caseous necrosis)
- Ghon complex:
- Combination of single lesion in lung + draining bronchial lymph node
- In healthy people, lesions heal & calcify –> seen on CXR
- Sometimes bacilli persist in granuloma for decades –> latent TB infection
5
Q
Primary TB infection
A
- Occurs in about 5-10% of cases within first 2 years post-infection in otherwise healthy individuals
- In immunocompromised:
- Cell-mediated immunity inadequate
- Macrophages unable to contain primary infection
- Possible consequence = bacterial spread to virtually all organs –> potentially fatal miliary (disseminated) tuberculosis
- Contagious bacterial infection spread from lungs to other parts of body through blood/lymph system
6
Q
Latent TB infection
A
- In healthy individuals exposed to TB, lesions heal and become fibrotic or calcified
- Can be seen on CXR as evidence of primary infection
- Actiated macrophages successfully able to kill or inhibit bacterial growth
- Mycobacteria are difficult to kill –> some organisms may persist within granuloma for decades
- Results in continued antigenic stimulation, possible reactivation of disease later in life
- Infection is controlled, cannot be spread to other people, shows no signs of active disease, considered clinically latent TB
7
Q
Secondary TB infection
A
- May occur by reactivation of mycobacteria that have been carried in body in latent form for any # of years
- Most common site of reactivation = apex of lung
- Most likely due to high oxygenation levels
- Reactivation can occur in any tissue harboring latent bacteria from primary infection
- Lesions slowly become necrotic –> caseous –> liquefactive
- Adjacent lesions can coalesce to form larger lesions, eventually penetrate bronchi
- Organisms grow intra- and extra-cellularly –> may reach very high densities
- Organisms discharged into bronchi can result in coughing, ultimately spread of bacteria to other humans
8
Q
M. tuberculosis survival within phagosome
A
- Infected bacilli that reach alveoli are ingested by phagocytosis, multiply unimpeded in resident alveolar macrophages
- Virulence of bacilli depends on ability to survive in activated & unactivated macrophages
- Interferes with membrane-controlled trafficking, arrests phagosome maturation at stage when no harm can be done to pathogen by host acidification, while delivery of nutrients by membrane bound vesicles is unimpeded
9
Q
Key players in phagosome maturation arrest
A
- PIM and ManLAM
- Resemble mammalian phosphatidylinositols (involved in vesicular trafficking)
- PIM
- Stimulates fusion between phagosomes & early endosomes
- Ensures continual nutrient supply to phagosomal compartment
- Man-LAM
- Inhibits phagosomal maturation
- SapM
- Protein produced by M. tuberculosis
- Cleaves late endosomal vesicular marker PIP-3-phosphate in phagosome membrane, preventing fusion with lysosomes
10
Q
Primary goal of tuberculosis control
A
- To identify active infectious cases, treat to stop transmission
- Next step: identify contacts with latent infections
- Then identify high-risk individuals with latent infections
- BCG vaccination helps prevent disseminated forms in kids in high prevalence areas
11
Q
Symptoms of active TB: pulmonary and systemic
A
- Active pulmonary TB
- Cough
- Chest pain
- Hemoptysis
- Active systemic TB
- Fever
- Chills
- Night sweats
- Appetite loss
- Weight loss
- Fatigue
12
Q
Frequency of extrapulmonary sx in active TB
A
- Most commonly affects lungs = 70% of cases
- Extrapulmonary symptoms = 20% of cases
- Pulmonary + extrapulmonary = 8% of cases
- Most common forms of extrapulmonary disease:
- Lymphatic 42%
- Pleural disease 18%
- Miliary 2-3%
13
Q
Detection of latent TB infection
A
- Mantoux tuberculin skin test (TST/PPD)
- 20% of pulmonary TB, 50% of disseminated will be negative
- Interferon gamma release assays (IGRAs)
- Measure release of IFN-gamma in whole blood in response to stimulation by various antigens
- More sensitive than TST
14
Q
Typical treatment for drug-sensitive TB
A
- “4 for 2 and 2 for 4” pattern
- 2 months of:
- Rifampin
- Isoniazid
- Pyrazinamide
- Ethambutol
- After 2 months, discontinue pyrazinamide
- As soon as drug-susceptibility is confirmed, stop ethambutol
- For another 4 months:
- Rifampin
- INH
- 6 months total of treatment
15
Q
Treatment regimen for latent TB
A
- 600mg rifampin daily x 4 months
- 900mg rifapentine 1x/week + 900mg INH 1x/week for 3 months
