Tuberculosis

Question 1

Is the disease burden from TB increasing or decreasing?

Answer 1

It is falling globally

Question 2

How bad is the TB epidemic?

Answer 2

• TB is the number 1 killer of communicable diseases.

- TB kills more than HIV and Malaria together.

Question 3

What are the vulnerable groups in the UK for TB?

Answer 3

• Those from high prevalence countries.
• Homeless, alcoholics, IDU’s, those with mental health problems and in prison.
• HIV positive, Immunosuppressed.
• Elderly, neonates, diabetics.

Question 4

Which mycobacteria can cause TB?

Answer 4

• M. tuberculosis, M. africanum, M. bovis.
• They are non-motile bacillus, very slow growing and aerobic.
• Uniquely has a very thick fatty cell wall.
• HOWEVER, not all acid and alcohol fast bacilli (AAFBs) are TB.

Question 5

How is TB transmitted?

Answer 5

• Airborne (pulmonary & Laryngeal TB spreads, the others not)
• Usually requires prolonged close contact.
• Outdoors mycobacteria is eliminated by UV radiation and dilution.

Question 6

What is the exception to the rule about hoe TB is spread?

Answer 6

• Exception is Mycobacterium bovis, which can be spread by consumption of unpasteurized infected cows’ milk (very uncommon in the U.K.)

Question 7

Immunopathology (immune responses) for TB

Answer 7

Activated macrophages > Epithelioid cells > Langhan’s giant cells

Accumulation of macrophages, epithelioid & Langhan’s cells > GRANULOMA

Central caseating necrosis (may later calcify)

Question 8

How is the Th1 cell mediated immunological response like a two edged sword?

Answer 8

• It eliminates/ reduces number of invading mycobacteria.

- Tissue destruction is a consequence of activation of macrophages.

Question 9

Features of primary infection of TB

Answer 9

• No preceding exposure or immunity.
• Mycobacteria spread via lymphatics to draining hilar lymph nodes.
• Usually no symtoms, can be fever, malaise.

Question 10

What does the primary infection progress to (in a small number 1%)?

Answer 10

It progresses to Tuberculous bronchopneumonia.

• Primary focus continues to enlarge - cavitation
• Enlarged hilar lymph compress bronchi, lobar collapse
• Enlarged lymph node discharges into bronchus

Question 11

What does the primary infection progress to (in a small number 1-3%)?

Answer 11

• Miliary TB (looked like millet seeds on autopsy) develops, with hematogenous spread of bacteria to multiple organs
• Fine mottling on X-ray, widespread small granulomata
• CNS TB in 10-30%

Question 12

What does the primary infection progress to (in the majority >85%)?

Answer 12

• Initial lesion + local lymph node (Primary complex)
• Heals with or without scar. May calcify (Ghon focus + complex)
• Associated with development of immunity to tuberculoprotein

Question 13

What are the two main hypothesis’ of post primary disease?

Answer 13

1. TB bacteria entering a dormant stage with low or no replication over prolonged periods of time.
2. Balanced state of replication and destruction by immune mechanisms.

Question 14

What are the clinical presentations of TB?

Answer 14

• Cough
• Fever
• Sweats (mainly at night)
• Weight loss
• All three symptoms
• CRP normal in 15%, ESR normal in 21%.

Question 15

What may be absent in the clinical presentations of TB?

Answer 15

• Fever absent in 37%
• Sweats absent in 39%
• Weight loss absent in 38%
• All three absent in 25%

Question 16

When would you consider CT post-primary TB?

Answer 16

• Normal Chest Xray but clinical suspicion
• Miliary TB
• Cavitation & other differential
• Lymphadenopathy, alternative diagnosis.
• Targets for BAL

Question 17

How would you diagnose active pulmonary TB using Chest Xray?

Answer 17

Primary TB:

• Mediastinal lymphadenopathy (mainly unilateral, 15% bilateral)
• Pleural effusion
• Miliary (hematogenous spread, 1-3%)
• Pneumonic lesion w/ enlarged hilar nodes- consider primary TB

Question 18

How would you get a bug sample for TB?

Answer 18

• Sputum; 3 samples, 8-24hrs gap, at least 1 early morning sample
• Induced sputum
• Bronchoscopy with BAL
• Endobronchial ultrasound (EBUS) with biopsy
• Lumbar puncture in CNS TB
• Urine in urogenital TB
• Aspirate/biopsy from tissue ( lymph-node, bone, joint, brain, abscess …)
• Mantoux or IGRA are NOT routinely used in diagnosing active TB

Question 19

What drugs are used to treat TB?

Answer 19

• Streptomycin
• Isoniazid
• Pyrazinamide
• Rifampicin
• Ethambutol

Question 20

Rules for the treatment of tuberculosis

Answer 20

• Multiple drug therapy is essential
• Single agent treatment leads to drug resistant organisms within 14 days.
• Therapy must continue for at least 6 months.
• TB therapy is a job for committed specialists only.
• Legal requirements to notify all cases.
• Test for HIV, Hepatitis B and C.

Question 21

What is the standard treatment for TB?

Answer 21

2 Rifampicin/Isoniazid/Ethambutol + 4 Rifampicin/Isoniazid

• Standard 70kg patient takes 12 tablets daily.
• 6 months duration
• Pyridoxine (Vitamin B6) with isoniazid to reduce risk of neuropathy
• Steroids (CNS, Milliar, Pericardial)
• Vitamin-D substitution ?

Question 22

What are side effects of Rifampicin?

Answer 22

• Orange ‘Irn Bru’ urine/tears/lenses
  Induces liver enzymes, prednisolone, anticonvulsants
• All hormonal contraceptive methods ineffective
• Hepatitis

Question 23

What are the side effects of Isoniazid?

Answer 23

• Hepatitis

- Peripheral neuropathy (pyridoxine B6)

Question 24

Who can get the BCG vaccination?

Answer 24

• Given selectively to risk groups since 2005
• Neonates, or unvaccinated children under 5, whose parents/grandparents were born in a country with an annual incidence of TB of 40/100,000 or greater
• Unimmunised contacts of cases
• Unimmunised high risk employees

Question 25

Who should get screened for latent TB (LTBI)?

Answer 25

- Contacts of people with active pulmonary or laryngeal TB who are aged ≤65 years (hepatotoxicity increases with age) - New entrants from high endemic areas - ‘Pre-biologics’ (TNF-alpha inhibitors) - Outbreaks

Question 26

What is the treatment for Latent TB (LTBI)?

Answer 26

- Rifampicin & Isoniazid for three months or - Isoniazid only for six months, or - Rifampicin only for six months, or - Rifapentine & Isoniazide once weekly for 12 weeks (underserved population).