Mycobacteria

Question 1

Physical description of mycobacteria

Answer 1

• acid fast rods
• very slow growth, from one pole only
• serpentine cord formation in vitro associated with virulence

Question 2

Cell wall of mycobacteria

Answer 2

• 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

Question 3

Resulting cytokines resulting from mycobacteria

Answer 3

• 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

Question 4

Clinical symptoms of mycobacterium tuberculosis

Answer 4

-fatigue, fever, night sweats, weight loss, cough w/blood tinged sputum(hemoptysis)

Question 5

Role of primary exudative lesion in mycobacterium tuberculosis

Answer 5

-primary exudative lesion: edema, inflammation, PMNLs
leads to
-heals
-necrotizes lung
-productive lesion leading to a granuloma

Question 6

Role of granuloma in the clinical presentation of TB

Answer 6

1. encased
   - reactivation leading to multiple granulomas, fibrinates lung
2. spread
   - via lymph, bronchi
   - via blood to liver, bone marrow, lungs(miliary TB)

Question 7

Resulting tissue from the formation of granuloma

Answer 7

-Caseum; necrotic tissue damaged by inflammatory response and lack of vascularization

Question 8

Epidemiology of TB

Answer 8

• 2B people in the world infected
• 95% asymptomatic
• at risk: minorities, immigrants, coexisting infections, homeless, very young or old, travelers

Question 9

Pathogenesis of TB

Answer 9

• 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

Question 10

Control of TB, PPD and IGRA assay tests

Answer 10

• 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

Question 11

Control of TB continued

Answer 11

• 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

Question 12

Control of TB with drugs

Answer 12

• 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

Question 13

Secondary drugs for drug resistant TB

Answer 13

-fluoroquinolones, aminoglycosides

Question 14

Treatments regimens for XDR-TB

Answer 14

• 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