Tuberculosis

Question 1

Bacterium causing tuberculosis

Answer 1

Mycobacterium tuberculosis

Question 2

How does tuberculosis normally present?

Answer 2

Chronic pneumonia

Question 3

Common symptoms of tuberculosis

Answer 3

Persistant productive cough
Persistant fever
Night sweats
Weight loss over several weeks/months

Question 4

Organ most commonly affected by tuberculosis

Answer 4

Lungs (86% of cases)

Question 5

When is tuberculosis infection recognised?

Answer 5

When the immune system contains the disease

Question 6

When is tuberculosis disease recognised?

Answer 6

When the bacterium evades the immune system

Question 7

Ranked infectious cause of death

Answer 7

Second, after HIV

Question 8

Pathogenic mycobacteria

Answer 8

M. tuberculae
M. bovis
M. ulcerans
M. leprae

Question 9

Symptoms of mycobacterium ulcerans

Answer 9

Skin lesions

Question 10

Symptoms of mycobacterium leprae

Answer 10

Leprosy

Question 11

Features of mycobacteria
1)
2)
3)
4)
5)

Answer 11

1) Aerobic
2) Acid fast
3) Resistant to drying
4) Very slow growing
5) Resistant to common antimicrobials

Question 12

Constituents of mycobacterial cell wall

Answer 12

1) Superficial lipids
2) Mycolic acid
3) Arabinogalactam
4) Lipoarabinomannan

SMAL

Question 13

Acid-fast staining technique
1)
2)
3)

Answer 13

1) Stain for ten minutes with carbol-fuschin
2 ) Wash completely with alcohol
3) Counterstain with a blue dye

Question 14

Colour that mycobacteria stain with an acid-fast stain

Answer 14

Pink

Other bacteria stain blue

Question 15

TB transmission

Answer 15

Aerosol

Question 16

Most infectious droplet size

Answer 16

Below 5 micrometers
Stay aerosolised for hours, can persist indefinitely in a dried state on surfaces
Evade mucociliary elevator

Question 17

How does M. tuberculae avoid macrophage microbicidal action?
1)
2)
3)

Answer 17

1) Lysosomal fusion inhibited by mycobacterial lipids
2) ROS neutralised by enzymes
3) NH4 produced, keeps pH~6.2, 6.3

Question 18

Alveolar macrophage response to phagocytosis of M. tuberculae
1)
2)
3)

Answer 18

1) Interleukin release
2) TNF release
3) CD4 T-cell activation

Question 19

Interleukins released by alveolar macrophages upon M. tuberculae phagocytosis

Answer 19

IL-1, IL-8, IL-12, TNFalpha

Question 20

Reason for chronic immune activation by M. tuberculae
1)
2)
3)
4)

Answer 20

1) APC induces Th1, Th17 differentiation
2) Th1 releases a lot of IFNgamma, TNF, Th17 recruit neutrophils
3) Recruited neutrophils and macrophages result in chronic inflammation
4) Macrophages and dendritic cells travel to lymph nodes, further activate Th and Tc cells.

Question 21

Effect of prolonged TB infection

Answer 21

Delayed-type hypersensitivity, granuloma formation

Question 22

Granuloma formation
1)
2)
3)
4)
5)

Answer 22

1) More IFNgamma results in greater macrophage activation
2) Greater macrophage activation results in more IL-8, IL-1, TNFalpha
3) More IL-8, IL-1 and TNFalpha results in greater endothelial activation, greater macrophage and lymphocyte migration to site of infection
4) More IL-1 leads to fever
5) More TNFalpha leads to weight loss, granuloma formation, death of some infected macrophages

Question 23

How do giant cells form?

Answer 23

Several macrophages fuse

Question 24

Effectiveness of granuloma formation

Answer 24

90% of cases contains infection

Question 25

Result of granuloma containment of tuberculosis

Answer 25

Latent tuberculosis

Question 26

Prevalence of primary tuberculosis

Answer 26

5% of cases

Question 27

Primary tuberculosis

Answer 27

Immune system fails to contain infection Worsening pneumonia Potential for bacteria to go systemic --> miliary TB

Question 28

Secondary tuberculosis

Answer 28

In those who initially control the infection, ~5-10% chance of reactivation of latent disease in 2 years

Question 29

Effect of active tuberculosis infection in the lungs

Answer 29

Caseous necrosis | Eventual liquefaction of lungs (cavitaiton).

Question 30

Mantoux test 1) 2)

Answer 30

1) Inject purified protein derivative (tuberculin) into skin | 2) If prior exposure, after 48-72 hours preformed memory T cells travel to site, produce inflammation, induration

Question 31

What does the Mantoux test screen for?

Answer 31

Infection, NOT disease

Question 32

Ways to test for TB infection 1) 2)

Answer 32

1) Mantoux test | 2) IFN production in vitro

Question 33

``` In vitro IFN production TB test 1) 2) 3) 4) ```

Answer 33

1) Patient blood sample taken, add culture medium 2) Add antigens specific to M. tuberculosis 3) Incubate for 24 hours 4) Test for IFNgamma secretions by memory T cells

Question 34

Lab diagnosis of active TB disease 1) 2) 3)

Answer 34

1) Chest X-ray 2) Acid-fast bacterial stain of sample (eg: sputum) 3) Culture of bacteria on enriched medium

Question 35

Issues with culturing TB 1) 2) 3)

Answer 35

1) Very slow-growing 2) Solid medium takes 4-8 weeks 3) Specialised liquid medium takes 7-14 days

Question 36

Antimicrobial therapy for active TB 1) 2) 3)

Answer 36

1) Six-month treatment 2) At least three anti-TB agents used: isoniazid, rifampicin, pyrazinamide, ethambutol for 2 months 3) Isonazid and rifampicin for a further 4 months

Question 37

Resistance to isonazid and pyrazinamide

Answer 37

Isonazid and pyrazinamide are activated by bacterial enzymes (KatG and pyrazinamidase) Mutations in these enzymes can confer resistance

Question 38

Treatment for latent TB

Answer 38

Isonazid for 6 - 12 months | Reduces reactivation by 60-90%

Question 39

BCG vaccine

Answer 39

Bacille Calmette Guerin vaccine | Long-term culture of M. bovis

Question 40

Issues with BCG vaccine

Answer 40

Almost 100% conversion to tuberculin positive 0-80% protection - extremely variable Negates the use of Mantoux test (tuberculin skin test)

Question 41

Where in the lungs does TB normally infect?

Answer 41

High up, as it needs oxygen

Question 42

Mean TB generation time

Answer 42

15-20 hours

Question 43

Main contributor to waxy cell wall

Answer 43

Mycolic acid

Question 44

Requirement for positive TB result

Answer 44

5 or more bacilli on a slide

Question 45

Location of hilar lymph node

Answer 45

Junction of lungs

Question 46

Medium used for TB culture

Answer 46

Lowenstein-Jensen medium

Question 47

Antibiotics used to treat TB

Answer 47

Rifampicin Isoniazid Pyrazinamide Ethanbutol