Mycobacteria Flashcards
Physical description of mycobacteria
- acid fast rods
- very slow growth, from one pole only
- serpentine cord formation in vitro associated with virulence
Cell wall of mycobacteria
- mycolic acids, C60-90 lipids, very hydrophobic
- acid fastness
- prevent attack by lysozyme, complement
- anchored to PG directly or via arabinogalactan/arabinomannan
- cord factor(trehalose-6,6-dimycolic acid) allows formation of cords, cytotoxic in mammals
Resulting cytokines resulting from mycobacteria
- Way part of outer layer; antigenic(Freund’s adjuvant)
- lipoarabinomannan(LAM): stimulates cytokine production by mammalian host
- TNF and IL6 stimulate replication of HIV long terminal repeats
Clinical symptoms of mycobacterium tuberculosis
-fatigue, fever, night sweats, weight loss, cough w/blood tinged sputum(hemoptysis)
Role of primary exudative lesion in mycobacterium tuberculosis
-primary exudative lesion: edema, inflammation, PMNLs
leads to
-heals
-necrotizes lung
-productive lesion leading to a granuloma
Role of granuloma in the clinical presentation of TB
- encased
- reactivation leading to multiple granulomas, fibrinates lung - spread
- via lymph, bronchi
- via blood to liver, bone marrow, lungs(miliary TB)
Resulting tissue from the formation of granuloma
-Caseum; necrotic tissue damaged by inflammatory response and lack of vascularization
Epidemiology of TB
- 2B people in the world infected
- 95% asymptomatic
- at risk: minorities, immigrants, coexisting infections, homeless, very young or old, travelers
Pathogenesis of TB
- always spread person to person via respiratory droplets
- attach to alveolar macrophages and invade
- prevent phagolysosome fusion
- cytotoxicity from cord factor
- cytokine mediated inflammation
- spread by cough and swallow elsewhere
- long term latency in granulomas and bone marrow stem cells
Control of TB, PPD and IGRA assay tests
- detection is critical, since Ig# of asymptomatic carriers
- PPD test, Tmem cells specific for TB present
- IGRA assay: test for release of interferon gamma from peripheral lymphocytes when stimulated by TB antigen
Control of TB continued
- culture takes 6-8wks
- acid fast sputum stain requires massive infection to detect
- best now is PCR based test with M.tub specific primers
- positive IGRA or PPD without sx and normal X-ray is LATENT TB
- latent TB must be treated
Control of TB with drugs
- INH, rifampin, pyrazinamde, ethambutol daily or biweekly for 6-9 months
- latent TB or family contact prophylaxis use just INH
- DOTS important for some patients
- MDR = INH + RIF
- XDR = MRD+FQ+2nd line resistance
Secondary drugs for drug resistant TB
-fluoroquinolones, aminoglycosides
Treatments regimens for XDR-TB
- beta lactams not good for myco TB because of beta lactamase black
- carbapenems not good substrates for BlaC
- Meropenem + clavulanate is effective against XDR TB
- linezolid is effective
- delamanid inhibits mycolic ac. synthesis
- bedaquiline inhibits mycobact. ATP synthase
