Tuberculosis Flashcards

1
Q

Bacterium causing tuberculosis

A

Mycobacterium tuberculosis

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2
Q

How does tuberculosis normally present?

A

Chronic pneumonia

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3
Q

Common symptoms of tuberculosis

A

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

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4
Q

Organ most commonly affected by tuberculosis

A

Lungs (86% of cases)

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5
Q

When is tuberculosis infection recognised?

A

When the immune system contains the disease

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6
Q

When is tuberculosis disease recognised?

A

When the bacterium evades the immune system

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7
Q

Ranked infectious cause of death

A

Second, after HIV

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8
Q

Pathogenic mycobacteria

A

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

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9
Q

Symptoms of mycobacterium ulcerans

A

Skin lesions

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10
Q

Symptoms of mycobacterium leprae

A

Leprosy

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11
Q
Features of mycobacteria
1)
2)
3)
4)
5)
A

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

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12
Q

Constituents of mycobacterial cell wall

A

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

SMAL

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13
Q

Acid-fast staining technique
1)
2)
3)

A

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

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14
Q

Colour that mycobacteria stain with an acid-fast stain

A

Pink

Other bacteria stain blue

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15
Q

TB transmission

A

Aerosol

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16
Q

Most infectious droplet size

A

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

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17
Q

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

A

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

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18
Q

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

A

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

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19
Q

Interleukins released by alveolar macrophages upon M. tuberculae phagocytosis

A

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

20
Q
Reason for chronic immune activation by M. tuberculae
1)
2)
3)
4)
A

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.

21
Q

Effect of prolonged TB infection

A

Delayed-type hypersensitivity, granuloma formation

22
Q
Granuloma formation
1)
2)
3)
4)
5)
A

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

23
Q

How do giant cells form?

A

Several macrophages fuse

24
Q

Effectiveness of granuloma formation

A

90% of cases contains infection

25
Q

Result of granuloma containment of tuberculosis

A

Latent tuberculosis

26
Q

Prevalence of primary tuberculosis

A

5% of cases

27
Q

Primary tuberculosis

A

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

28
Q

Secondary tuberculosis

A

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

29
Q

Effect of active tuberculosis infection in the lungs

A

Caseous necrosis

Eventual liquefaction of lungs (cavitaiton).

30
Q

Mantoux test
1)
2)

A

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

31
Q

What does the Mantoux test screen for?

A

Infection, NOT disease

32
Q

Ways to test for TB infection
1)
2)

A

1) Mantoux test

2) IFN production in vitro

33
Q
In vitro IFN production TB test
1)
2)
3)
4)
A

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

34
Q

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

A

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

35
Q

Issues with culturing TB
1)
2)
3)

A

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

36
Q

Antimicrobial therapy for active TB
1)
2)
3)

A

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

37
Q

Resistance to isonazid and pyrazinamide

A

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

38
Q

Treatment for latent TB

A

Isonazid for 6 - 12 months

Reduces reactivation by 60-90%

39
Q

BCG vaccine

A

Bacille Calmette Guerin vaccine

Long-term culture of M. bovis

40
Q

Issues with BCG vaccine

A

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

41
Q

Where in the lungs does TB normally infect?

A

High up, as it needs oxygen

42
Q

Mean TB generation time

A

15-20 hours

43
Q

Main contributor to waxy cell wall

A

Mycolic acid

44
Q

Requirement for positive TB result

A

5 or more bacilli on a slide

45
Q

Location of hilar lymph node

A

Junction of lungs

46
Q

Medium used for TB culture

A

Lowenstein-Jensen medium

47
Q

Antibiotics used to treat TB

A

Rifampicin
Isoniazid
Pyrazinamide
Ethanbutol