Dr. Behr -- Tuberculosis

Question 1

Define tuberculosis

Answer 1

The diseased state:

• Actively replicating bacteria
• Contagious, culture positive

Question 2

Define tuberculous infection

Answer 2

The carrier state

• Clinically latent (latent TB infection/LTBI)
• Non-infectious, tuberculin positive

Question 3

Bacteria responsible for tuberculosis and tuberculous infection

Answer 3

Mycobacterium tuberculosis

Question 4

Cause of avian TB

Answer 4

Mycobacterium avium

Question 5

Hypothesized cause of Crohn’s disease

Answer 5

M. avium paratuberculosis

Question 6

Environmental bacterium that causes TB-like disease in miners with silicosis

Answer 6

M. kansasil

Question 7

Cause of leprosy

Answer 7

M. leprae

Question 8

Place of origin of M. tuberculosis and its geographic journey (4)

Answer 8

1. Africa
2. Paleo-migration –> Europe (by foot)
3. Colonization of Americas (by ship)
4. Fur trade = All across Canada (by canoe)

Question 9

What kind of organism is M. tuberculosis (i.e. its behavior with humans)

Answer 9

• Pathogen
• Symbiont

Question 10

How is *M. tb *an educated pathogen?

Answer 10

• Localized, chronic pathology = ambulatory host and transmission
• (As opposed to organisms such as Legionella pneumonia, which is a diffuse, fast disease with a very sick host and no transmission)

Question 11

3 potential outcomes after TB exposure and their respective frequencies

Answer 11

1. No infection
   
   • `(?; 2/3 don’t test +)
2. Infection, no disease
   
   • (90% if immune status OK)
3. Infection, disease +/- death
   
   • 5% in 2 years
   • 5% in rest of life

Question 12

3 reasons why a few progress to TB

Answer 12

• Age (infants)
• Acquired immune deficiency
  
  • HIV+, steroids, Anti-TNF
• Natural immunity
  
  • Genetics: people who progressed 1st time and are cured = 5x higher rate of TB than community

Question 13

Where *M. tuberculosis *ends up in the human body

Answer 13

Alveoli of lungs (in alveolar macrophages)

Question 14

2 options for the outcome of *M. tb *in alveolar macrophages

Answer 14

1. Kill bacteria on contact –> no infection, tuberculin -
2. Permit bacterial infectoin (Ghon focus)
   
   • Infection
   • TB positive
   • Attraction of other cells to aggregate –> granuloma

Question 15

3 components of a granuloma

Answer 15

1. Macrophages
2. Lymphocytes
3. Fibrous ring

Question 16

How does *M. tb *end up in hilar lymph nodes?

Answer 16

Dendritic cells via lymphatics

Question 17

2 options for the outcome of *M. tb *in hilar lymph nodes

Answer 17

1. Chronic localized lymphadenitis
2. Further spread

Question 18

2 ways that TB can further spread if in hilar lymph nodes

Answer 18

1. Up lymphatics via thoracic ducts –> hematogenous seeding
2. Through lymphatics, within lungs –> areas of lowest vacular perfusion (apex)

Question 19

Non-transmissible TB

Answer 19

TB meningitis

Question 20

M. tb reservoir host

Answer 20

Human (rarely from animals)

Question 21

% of world’s population infected by M. tb

Answer 21

1/3

Question 22

Cause of death in ~25% of AIDS

Answer 22

TB

Question 23

Strongest risk factor for progression of TB infection to disease

Answer 23

HIV infection

Question 24

4 general clinical manifestations of TB

Answer 24

1. Fever
2. Sweats
3. Weight loss
4. “Consumption”

Question 25

2 contagious organ specific clinical manifestations of TB

Answer 25

Pulmonary * Cough * Sputum +/- blood

Question 26

5 organ-specific non-contagious clinical manifestations of TB

Answer 26

1. Scrofula = swollen lymph nodes 2. Genitourinary = sterile pyuria 3. Bone = back pain, fracture, "hump-back" 4. Meningitis = headache, obtundation 5. Miliary TB (no obvious site)

Question 27

Number of sputum specimens for smear exam and culture

Answer 27

3

Question 28

3 things to do if patient is unable to cough up sputum

Answer 28

* Induce sputum (kids too) * Bronchoscopy * Gastric aspiration

Question 29

Positive AFB smear

Answer 29

Red rods = tubercle bacilli

Question 30

Purpose of cultures in TB diagnosis and how long results take

Answer 30

* Confirmation * 2 - 3 weeks

Question 31

Compare PCR sensitivity to other forms of TB diagnosis

Answer 31

* Better than microscopy * Not as good as culture

Question 32

2 situations where PCR use is appropriate in TB diagnosis

Answer 32

1. AFB smear + and want quick answer to what bacteria is present 2. New, rapid test by Cepheid for developing world (including Nunavik)

Question 33

2 situations where PCR has limited utility in TB diagnosis

Answer 33

1. AFB smear negative 2. Non-pulmonary sample

Question 34

Length of short course treatment for TB

Answer 34

24 weeks

Question 35

3 points for prioritizing TB control

Answer 35

1. Identify and treat active TB to reduce # of contagious persons 2. Identify contacts of cases, test for infection, provide chemoprophylaxis 3. Identify people with patent infection as potential candidates for chemoRx

Question 36

2 possible causes of a false-positive PPD

Answer 36

1. Nontuberculous mycobacteria 2. BCG vaccination

Question 37

5 possible causes of false-negative PPD

Answer 37

1. Anergy 2. Recent TB infection 3. Very young age (\<6 months old) 4. Live-virus vaccination 5. Overwhelming TB disease

Question 38

New test for TB detection

Answer 38

IFN-gamma release assays

Question 39

Platform of IFN-gamma release assays

Answer 39

From skin to lab ELISA

Question 40

Advantage of IFN-gamma release assays

Answer 40

Specificity in face of BCG vaccination

Question 41

Disadvantage of IFN-gamma release assays

Answer 41

Poor reproducibility

Question 42

LTBI treatment

Answer 42

Isoniazid for 9 months

Question 43

Efficacy of BCG vaccination against peditric TB

Answer 43

80%