Tuberculosis

1
Tuberculosis

• the major human respiratory infection throughout
  the world
• 20 million active cases of TB in the world
• One third of the world population (1.7 billion
  persons) are infected with the TB bacillus

2
Characteristics of the organism

• acid-fast bacillus that is not motile, and does
  not form spores, nor secrete toxins
• intracellular, aerobic, hydrophobic
• reproduces slowly, and requires high levels of
  oxygen in order to divide and metabolize

3
Mycobacterium tuberculosis

• Without oxygen, enters a dormant state, either
  inside cells or in extracellular caseous material
  in lungs
• Able to develop resistant strains (major problem)
  through mutations
• Resistance differs according to population
  characteristics (sanitation, poverty, poor health
  care, drug abuse (high rate resistance in NYC)

4
Infectious Process

• Inhaled as droplets into lungsvery few organisms
  needed to infect
• Bacilli ingested by alveolar macrophages in a
  typical phagocytic process
• Phagocytosis faultythe organisms actually
  survives inside the phagolysome
• Host kills infected macrophagesproducing caseous
  tissue

5
Infectious Process

• a constant battle between host defenses and the
  evasive properties of the microorganism in TB
  cannot grow and divide in caseous tissuesbut
  liquefied cavity in middle does provide an
  environment for TB bacilli to divide

6
Lesions

• Exudative and Proliferative
• Exudative inflammatory lesions heavily
  infiltrated with polymorphonuclear leukocytes,
  monocytes, and lymphocytes and producing a
  fibrinous exudate
• Proliferative Clssic granulomatous lesions

7
Lesions

• Tubercles seen on xray under microscope rings
  of macrophages other inflammatory cells
  surrounding infected cells. Caseous (solid
  cheese-like material) in middle

8
Stages of Infection

• Stage I (day 1 to 7 after infection)
• resident alveolar macrophages attack organisms
  through phagocytosis
• Bacilli may be killed at this point, arresting
  the disease
• Or Bacilli released from macrophages, which
  starts Stage II

9
Stages

• Stage II (days 7 to 21 ) symbiosis
• Macrophages from blood enter lung tissue
• Tubercles form
• Living bacilli divide and grow in number

10
Stages

• Stage III
• bacterial growth slowed because of both
  cell-mediated immunological activities delayed
  type hypersensitivity responses
• tubercle now becomes a solid caseous lesion
• Decreased replication in caseous tissue because
  of anoxia
• Many tubercles become sterile..calcified and
  fibrotic
• Others may contain living organisms in suspended
  animation

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Stages

• Stage IV
• liquefaction of the center of the caseous
  granuloma occurs
• This allows organisms to receive enough 02 to
  start dividing again
• Ineffective immune response to huge numbers of
  microorganisms produced
• Cavitation occurs, releasing organisms

12
Stages

• Primary infection occurs in the lungs, and may
  produced calcified tubercle (95 of cases
  arrested here)
• Most often, does not cause acute Sx, but develops
  insidious infection or sets stage for future
  secondary infection
• Secondary (post-primary)infection most common
  form of TB in adults

13
Immunology of TB

• After macrophages ingest TB bacilli, process and
  present to T cells in association with MHC II
• IL-1 released, T cells recruited
• Th-1 cells stimulated, release pro-inflammatory
  cytokines which stimulate resting resident
  macrophages
• Macrophages continue to release cytokines into
  lung
• Th-2 cells, NK cells, and neutrophils also
  recruited into lung

14
Immunology

• Positive tuberculin test is a delayed
  hypersensitivity reactionmay take 10 weeks after
  infection before it becomes positive
• False positives and negatives are possible

15
Clinical Presentation

• Sx almost always are pulmonary cough,
  hemoptysis, chest pain
• Systemic Sx include fatigue, weight loss, fevers,
  night sweats, these symptoms probably due to
  cytokinesespecially TNF-alpha

16
Treatment

• Clinical presentation
• Positive skin test with negative chest X-ray
• Household contacts of patients with active TB
• Active TB with negative sputum smear and culture

• Therapy
• isoniazid prophylactic therapy (300 mg per day)
  for 6-12 months
• isoniazid and rifampin therapy for 4 months
• Initial phase isioniazid, rifampin,
  pyrazinamide for 2 mos. Then isoniazid and
  rifampin for 4 mos. Minimal length of treatment
  is 6 mos.
• Initial phase isioniazid, rifampin, and
  pyrazinamide for 2 mos. Followed by isoniazid and
  rifampin for 4 mos..
• Patients who have failed therapy or have relapsed
• Repeat susceptibility testing for resistance.
• Retreatment with an initial daily phase of
  isoniazid, rifampin, pyrazinamide, ethambutol,
  and streptomycin for 2 mos followed by the same
  drugs minus streptomycin for an additional 1 mo,
  then 5 mos of therapy with isonizaid, rifmaopin,
  and ethambutol given 3 times per week or daily.
•  

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Treatment

• Patients with positive cultures
• Patients who have failed therapy or have relapsed

• isioniazid, rifampin, pyrazinamide for 2 mos
  isoniazid and rifampin for 4 mos.
• Repeat susceptibility testingRetreatment with
  isoniazid, rifampin, pyrazinamide, ethambutol,
  and streptomycin for 2 mos 5 mos of isonizaid,
  rifmaopin, and ethambutol given 3 times per week
  or daily.

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website

• http//www.cpmc.columbia.edu/resources/tbcpp/extre
  s.html
• For resource information on tuberculosis