Lecture 12: TB

Question 1

What is the pathogenesis of TB?

Answer 1

Airborne droplet spread

Inhaled – deposited in terminal airspaces

Macrophages ingest bacilli – replicate within endosomes

Transported to regional lymph node

Question 2

What are the four outcomes of TB that has spread to lymph nodes?

Answer 2

Killed

Multiply → primary TB

Dormant → asymptomatic (LTBI if exposed to host immune system)

Proliferate after period of latency → reactivation disease

Question 3

What is the % risk of developing TB over a lifetime?

Answer 3

5-10%

This is considerably increased for those with immunodeficiency

Question 4

What do we know about the TB bacteria?

Answer 4

Aerobic bacillus

Divides every 16-20 hours (slow)

Cell wall, but lacks phospholipid outer membrane

Does not stain strongly with Gram stain (weakly positive)
Retains stains after treatment with acids

Acid fast bacillus

Question 5

What is meant by granulomatous inflammation?

Answer 5

Rim of lymphocytes

Fibroblasts

Central infected macrophages (giant cells)

Central necrosis – caseation

Secretion of cytokines (IFNγ) – activate macrophages to kill bacteria

AFBs in granulomas

Question 6

What can be used to visualise M.tuberculosis?

Answer 6

Ziehl-Neelsen stain - bright red bacilli on blue background

Auramine-rhodamine stain

Fluorescent microscopy

Question 7

What may increase the risk of transmission?

Answer 7

Close contacts of infectious cases

Contact with high risk groups

Immune deficiency

Lifestyle factors

Genetic susceptibility (twin studies of gene polymorphisms)

Question 8

What are some causes for immune deficiency?

Answer 8

HIV
Steroids
Chemotherapy and biologics
Nutritional deficiency (vit D), 
Diabetes
End stage renal failure

Question 9

What lifestyle factors may increase the risk of getting TB?

Answer 9

Drug / alcohol misuse

Homelessness / hostels / overcrowding

Prison inmates

Question 10

What % of cases are primary TB?

Answer 10

1-5%

Bacilli overcome immune system soon after initial infection

Question 11

What % of cases are latent TB?

Answer 11

2-23% cases – reactivation disease

Risk of reactivation increases with immunosuppression
HIV + risk 10% per year
HIV – risk 1%

Question 12

How can you diagnose active TB?

Answer 12

Identify the infected area

Isolate the organism

Obtain information regarding susceptibility to antibacterials

Question 13

How can you diagnose latent TB?

Answer 13

Identify immune response to TB proteins or TB-specific antigens

Question 14

What is the basis for the mantoux test?

Answer 14

Circulating memory T-lymphocytes ability to mount a delayed hypersensitivity reaction

Question 15

What are the problems with the mantoux test?

Answer 15

Cross reactive with other Mycobacterial antigens so non-specific

Maybe be falsely negative in severely ill or immunosuppressed individuals

Question 16

What can be used as an alternative to mantoux?

Answer 16

ELISPOT/ELISA: Enzyme linked immunological assay of release of interferon-gamma in whole blood following stimulation by specific tuberculosis antigen

Question 17

What are the advantages and problems with the ELISA test for TB?

Answer 17

Advantages:

• More specific than Mantoux
• Correlates better with degree of exposure than Mantoux

Problem:
- Does not differentiate between latent infection and disease

Question 18

What % of cases are pulmonary TB?

Answer 18

55%

Question 19

What are the clinical features of pulmonary TB?

Answer 19

Cough
Weight loss
Haemoptysis
Fever
Chest pain
Night sweats

Question 20

How can you diagnose pulmonary TB?

Answer 20

Chest imaging

Sputum/BAL

Question 21

What sites may be affected by extra pulmonary TB?

Answer 21

Lymph nodes
CNS
Bone (Pott’s disease of the spine)
Genitourinary system
GI tract
Disseminated/miliary

Question 22

What is TB lymphadenitis?

Answer 22

Infection of LN

Often get worse on treatment - paradoxical reaction

Can form sinus tracts with chronic discharge

Cold abscess formation

Question 23

What are the symptoms of miliary TB?

Answer 23

Fevers, sweats, weight loss and malaise very common

Respiratory symptoms in majority

GI or CNS symptoms in 20% (abdo pain, diarrhoea, hepatomegaly in 50%, headache or confusion - altered mental state in 20%)

Question 24

What is the standard pharmacological treatment of TB?

Answer 24

2 months (initial phase) of Isoniazid, Rifampicin, Pyrazinamide and Ethambutol

Followed by:
4 months (continuation phase) of Isoniazid and Rifampicin

Question 25

How must the standard pharmacological treatment be taken?

Answer 25

All together on an empty stomach 1 hour before breakfast; compliance is essential for cure.

Question 26

What about the treatment changes if there is CNS involvement?

Answer 26

The continuation phase of treatment is extended to 10 months making a 12 month full treatment plan

Question 27

What are the side effects of pyrazinamide?

Answer 27

Nausea
Skin rashes
Hepatoxicity
Joint pain
N&V

Question 28

What are the side effects of rifampicin?

Answer 28

Nausea
Skin rashes
Hepatoxicity
Reddish colour to urine

Question 29

What are the side effects of isoniazid?

Answer 29

Nausea
Skin rashes
Hepatoxicity
Fever 
Peripheral neuropathy 
Optic neuritis

Question 30

What are the side effects of ethambutol?

Answer 30

Nausea
Skin rashes
Peripheral neuropathy 
Optic neuropathy
Gout

Question 31

What is the order of most hepatoxicity to least?

Answer 31

Pyrazinamide
Rifampicin
Isoniazid