TB

Question 1

What is TB

Answer 1

Tuberculosis (TB) is a granulomatous disease caused by Mycobacterium tuberculosis.

Question 2

Epidemiology of TB

Answer 2

• 1.7 billion people worldwide have latent TB
• Common in South Asia and sub-Saharan Africa
• Prevalent in immunocompromised individuals

Question 3

RFs of TB

Answer 3

• Contactwith a person with active TB
• Endemic regions:South Asia or sub-Saharan Africa
• Homelessness
• Alcohol or drug abuse
• Immunocompromised: e.g. secondary to HIV, steroid use, malnutrition, immunosuppression medication
• M.bovis (animals) can cause abdominal TB

Question 4

Why do macrophages struggle to clear M. tuberculosis?

Answer 4

due to its waxy mycolic acid capsule which confers protection (the waxy membrane also prevents binding with normal stains - known as acid fastness).

TB very slow dividing bacteria with high oxygen demands

Question 5

How does TB spread?

Answer 5

via respiratory droplets from patients with active disease. After primary infection, immunocompetent patients can harbour the infection and remain asymptomatic (latent TB)

Question 6

What happens in immunocomprised patients with TB?

Answer 6

reactivation and failure to contain the bacteria can manifest as secondary TB. It can then spread systemically, resulting in miliary TB.

Question 7

What happens in primary TB?

Answer 7

1 initial exposure of tb with alveolar macrophage
2 macrophage attempts to form a phagosome but tb has protein which inhibits this
3 weeks later a granuloma form known as a ghon focus , the contents become necrotic
4 ghon focus and Hilar lymph nodes = ghon complex
5 on CXR seen as ranke complex

Question 8

What type of hypersensitivity reaction is a granuloma with caseous necrosis in centr?

Answer 8

Type IV

Question 9

What happens in Latent TB?

Answer 9

• This occurs after primary infection.
• Patients remain asymptomatic and the bacteria remains dormant, resulting innegative sputumcultures but apositive Mantoux test.
• These patients arenotinfectious.
• However, if patients areimmunocompromised, the disease can progress or reactivate at a later stage to becomeactive TB.
• Maybe tiny granulomata that become calcified
• detectable CMI to TB on tuberculin skin test

Question 10

What happens in secondary infection?

Answer 10

• Immunocompromised patients may develop secondary TB when latent TB reactivates, resulting in clinical features e.g. haemoptysis and fever.
• Patients are infectious.
• Reactivation typically occurs in thelung apexwhere pO2is highest, as mycobacteria are aerobic.
• The bacteria can spread locally, to form caseating granulomata, or systemically (miliary TB).

Question 11

What happens in Miliary TB?

Answer 11

This occurs due to lympho-haematogenous spread to multiple organs e.g. heart, lungs, spleen, liver, bone marrow, pancreas and brain.

Question 12

2-5% of people develop clinically evident primary pulmonary disease - what are the features

Answer 12

As granuloma grows it develops into a cavity.
More likely in apex of lung as there is more air and less blood supply / immune cells
The cavity is full of TB bacilli, which are expelled when patient coughs
Bacilli + macrophages coalesce to form a granuloma, this is called the Primary (Ghon) focus
mediastinal lymph nodes enlarge.
Primary focus + mediastinal LN = Ghon Complex

Question 13

S + S of TB

Answer 13

Auscultation - crackles may be present
Clubbing
Cough
Dyspnoea
Chest pain
Fever
Lethargy
Malaise
Anorexia

Question 14

Extra pulmonary Tmanifestations for TB

Answer 14

CNS - TB meningitis, CN palsy
Heart - pericardial TB
Adrenals - Addisons
Liver - hepatitis
GI - ascites, ileal malabsorption
Bone - pain or swelling of joint, Potts disease + spinal cord lesion
Genito-urinary TB - epididymitis, dysuria, haematuria

Question 15

Investigation for Latent disease of TB?

Answer 15

Mantoux screening - used to look for previous immune response to TB -

Interferon- gamma release assay (IGRA) - sample of blood and mixing it with antigens from TB in bacteria - more sensitive than Mantoux - used if Mantoux positive or inconclusive or if Mantoux falsely negative

Question 16

Mantoux Test/ TST tuberculin skin test

Answer 16

Antigenic protein derived from Mtb surface
injected intradermally (technically difficult)
stimulates ‘type 4 delayed hypersensitivity’ reaction

Antigen Presenting Cell takes up antigen and presents this to T cells
if Mtb specific memory T cells present they produce cytokines (IFNy) that cause local inflammatory reaction

Question 17

What are the problems with the mantoux test

Answer 17

Less sensitive in immunosuppressed or miliary TB (false negatives)
only moderately specific (false positives) e.g. if prior BCG
And
Won’t distinguish latent TB infection from active TB disease and a negative does not rule out active TB

Question 18

Interferon gamma release assays (IGRAs)

Answer 18

Stimulates memory T cells with antigens specific to M. tuberculosis ESAT-6 and CFP10
If TB specific memory T cells are present, they react by producing IFN-g
so detects real TB exposure and not just BCG (Bacille-Calmette-Guerin) live attenuated version of TB used in vaccination
98-99% specific – better than TST but still a risk of false positive depends on background exposure risk

Question 19

Chest X- RAY for active disease

Answer 19

• Primary TBmay show patchy consolidation, pleural effusions and hilar lymphadenopathy
• Latent disease may show ghon complex
• Reactivated TBmay show patchy or nodular consolidation with cavitation (gas filled spaces in the lungs) typically in the upper zones
• DisseminatedMiliary TB show “millet seeds” uniformly distributed throughout the lung fields

Question 20

Other than Chest x-ray what other tests can be done for Active disease?

Answer 20

• Microbiology/ microscopy- Definitive, AFB PCR CULTURE:send three deep cough sputum samples; analyse with Ziehl-Neelsen stain (will turn red) and Mycobacterium culture
  
  • Bronchoscopy with lavage if sputum can’t be obtained
  • Lymph node aspiration for biopsy
• Nucleic-Acid Amplification Test (NAAT): rapid diagnostic test conducted on sputum or urine if specific criteria are met e.g. co-existing HIV, risk of multi-drug resistance or, aged < 15 years
• HIV and hepatitis status:assess for co-infection

Question 21

What vaccine is given for TB?

Answer 21

BCG vaccine: intradermal injection of live attenuated (weakened) TB.

Question 22

Latent TB Management

Answer 22

• Isoniazid + Rifampacin 3 months : People <35 if hepatotoxicity is concer
• Isoniazid 6 months: interaction with rifampacin are a concern
• Pyridoxine

Question 23

Active TB management

Answer 23

• Notify within 3 days
• Contract tracing
• Isolate in negative pressure rooms
• RIPE : rifampicin, isoniazid, pyrazinamide and ethambutol 2 months
• Continuation phase: R + I for 4 months

Question 24

What happens if the TB is multi drug resistant?

Answer 24

treatment will be extended for 1-24 months, with at least six drugs

Rifampicin and Isoniazid +/- any others
Rifampicin monoresistance effectively same as Rifampicin so critical

Pyridoxine (Vit B6)

Question 25

Extreme drug resistance TB

Answer 25

MDR + second line drugs such as fluoroquinolones

Question 26

Extrapulmonary management

Answer 26

Usually longer continuation phase of antibiotics + corticosteroids

Question 27

Complications of TB

Answer 27

- **Empyema** - **Aspergilloma** - **Bronchiectasis** - **Pneumothorax:** TB is a cause of secondary spontaneous pneumothorax - **Miliary TB:** - Extrapulmonary diseases

Question 28

Rifampicin

Answer 28

Inhibits bacterial RNA polymerase - prevents transcription of DNA to mRNA SE: red urine, hepatitis, flu like symptoms

Question 29

Isoniazid

Answer 29

- Inhibits mycobacterial cell wall synthesis - SE: hepatitis, peripheral neuropathy, agranulocytosis

Question 30

Pyrazinamide

Answer 30

- Bactericidal initially, less effective later - Hepatitis - Gout - due to hyperuricaemia - Arthralgia and myalgia

Question 31

Ethambutol

Answer 31

- Causes inhibition of mycobacterial cell wall synthesis - Optic neuritis - Requires dose adjustment in renal impairment

Question 32

Pott's disease of the spine

Answer 32

This patient has presented with Pott's disease, or tubercular spondylitis, one of the commonest extrapulmonary manifestations of tuberculosis. Risk factors for infection with tuberculosis include prolonged exposure to poor living conditions and being immunocompromised. Clinical features include localised back pain, neurological deficits and radiographic findings indicative of vertebral body involvement. A biopsy demonstrating granuloma formation is highly suggestive of a tubercular process.