24: Tuberculosis

Question 1

Describe the species constituting the Myobacterium tuberculosis complex.

Answer 1

• Mycobacterium tuberculosis
• Mycobacterium bovis (unpasteurized milk/cheese)
• Mycobacterium africanum & canetti
• Mycobacterium microti: rodents

Question 2

Describe the characteristics of mycobacterium.

Answer 2

• Aerobic, non-motile, non-spore forming GPR
• Cell wall content is lipid
• Slow growth (20 hours)
• Length of rx = 6 months

Question 3

Describe the pathogenesis of mycobacterium.

Answer 3

TRANSMISSION

1. Lungs = entry portal (except M. bovis); inhale droplet nuclei; sneezing best; inoculum size, strain virulence and ventilation key to transmission enhancement
2. Primary infection (before immune response): TB reaches alveoli, replicates extra/intracellularly; multiplies for weeks, both in initial focus in alveolar
   macrophages and in cells transported lymphohematogenously
   throughout body

IMMUNE RESPONSE (6-12 weeks)

1. Must have intact immune system (CD4 cells)
2. Infected alveolar macrophage secretes IL-12, 18, which attract CD4 cells –> transformed CD4 –> proliferate, cutaneous hypersensitivity (PPD test), release IFN-gamma
3. IFN-gamma stimulates additional macrophage phagocytosis of M. tuberculosis, macrophage release of TNF-alpha
4. TNF-alpha increases macrophage killing ability, necessary for granuloma formation

PATHOLOGY

1. Granulomas sequester mycobacteria and prevent uncontrolled dissemination; epitheliod cell & langhans giant cells)
2. Small antigen load & high hypersensitivity key

Question 4

What is Primary Infection with Resolution?

Answer 4

• Occurs in 85% of cases
• Patient asymptomatic/mild viral syndrome
• Enlargement of hilar/peri-bronchial nodes
• Calcified granuloma on CXR = TB infx
  successfully contained
• Positive PPD 6-12 weeks

Question 5

What is Primary Infection with Progression?

Answer 5

PROGRESSIVE PRIMARY DISEASE

• Young children (>5yo) cannot resolve initial infx; progression to active disease, miliary or disseminated, CNS involvement
• Common in developing countries where TB is endemic
• TB pleurisy: hypersensitivity rxn, exudative pleural effusion, culture negative

PRIMARY INFX IN ADOLESCENCE/YOUNG ADULTS

• Results in upper lobe, adult cavitary disease (23% 15-19yo)

AIDS NOSOCOMIAL OUTBREAK

• UnDx pt w/ active TB in ward where all pt CD4<50
• No CD4s to mobilize, so no interferon gamma
• Rapid dissemination and death
• MDR strains killed scores in wards

Question 6

Describe reactivation of TB.

Answer 6

• Persistence of viable organisms.
• Occurs when cellular immune system can no longer contain MTB.
• Due to:
  
  • Iatrogenic immunosuppresion (transplant, rheumatologic Rx)
  • Immunocompromising disease
  • Malnutrition
  • Old age
• 85% of reactivation occurs in lungs
  
  • Caseating necrosis, liquefaction, drainage into bronchial tree; cavity formation
  • 5-6 logs greater bacillary multiplication in cavity vs. non-cavitary disease

Question 7

What is scrofula?

Answer 7

• Most frequent form of extrapulmonary TB
• Lymph nodes; usually cervical, supraclavicular, or axillary

Question 8

What is Potts Disease?

Answer 8

• Spinal involvement in TB
• From hematogenous spread from initial infection, lymphatic spread from pleural disease, or contiguous disease
• Spreads to intervertebral disk and adjacent vertebra

Question 9

What are the symptoms of TB?

Answer 9

• Systemic: fever, fatigue, night sweats, weight loss
• Pulmonary: cough (productive or dry), hemoptysis

Question 10

How is TB diagnosed?

Answer 10

• Sputum smear (acid fast, Ziehl-Neelsen, auramine)
• Culture (gold standard): liquid (1-3 wk); ID using DNA porbes and biochemical tests; necessary to determine abx
• NAAT (developed world only)
• CXR (upper lobe infiltrate w/wo cavity; hilar adenopathy w/wo infiltrates; pleural effusion; lower lobe infiltrate; miliary pattern)

Question 11

How is TB treated?

Answer 11

• Begin with 4 drugs, pending sensitivities
  
  • Rifampin (RMP): inhibits RNA polymerase; enables short course treatment (6-9 mo vs 18-24
    mon w/ non-RMP regimens); orange excretions; drug-drug intx (take protease inhibitor)
  • Isoniazid (INH): inhibits synthesis of mycolic acids (cell wall); add pyridoxine for pts w/ peripheral neuropathy, pregnant
  • Pyrazinamide (PZA): enables shortening of regimen from 9 to 6 mo; weight-dependent; contraindicated in pregnancy; give NSAIDS if arthralgias develop
  • Ethambutol (EMB): use in drug resistance and situations where INH or RMP cannot be used; may cause retrobulbar neuritis (colorblindness); drop when sensitivities known
• Directly Observed Therapy
• MDRTB Cocktail: resistance to both INH and RMP: 24 months; poor prognisis

Question 12

What is the prophylaxis for TB?

Answer 12

• Used in latent TB infections
• Targeted testing: PPD test in immunocompromised individuals
• Positive PPD:
  
  • 5mm: HIV infected, close contacts of infectious case, CXR evidence of old disease
  • 10mm: everyone else
• Tx = INH for 9 mo
• ELISPOT: indicates if reactivity represents tuberculosis infection, not BCG (vaccine)