TB

Question 1

Describe features of mycobacterium tuberculosis

Answer 1

• weakly gram-positive
• acid-fast bacilli = resistant to decolourising by acids once stained
• slow-growing
• produces white coloured colonies

Question 2

What are the 4 populations of M. Tuberculosis?

Answer 2

• actively growing organisms (can be killed by isoniazid)
• semi-dormant organisms inhibited by acid environment (can be killed by pyrazinamide)
• semi-dormant with spurts of active metabolism (killed by rifampicin)
• completely dormant organisms (not killed with standard drugs) - latent disease susceptible to transformation

Question 3

Describe the pathogenesis of TB infection

Answer 3

• TB bacteria is spread through the air (coughing/speaking)
• person inhales bacteria
• cavitary TB: cavities open into the bronchi containing the infection and allowing further spread
• TB lesion forms in the lung (Ghon complex): can spread to other tissues through haematogenous spread or become reactivated as a lung disease (eg. After immunosuppression/HIV/smoking)

Question 4

Describe the TB granuloma

Answer 4

• inflammatory cell infiltrate of immune cells which represents a non-replicating TB infection (what allows the infection to lay dormant)
• however provides a survival niche for the infection which can allow it to be reactivated and spread

Question 5

Describe how a TB granuloma can become resolved

Answer 5

• balanced state
• macrophages in the granuloma undergo differentiation into further specialised cells (foamy macrophages and giant cells)
• adaptive immune system results in periphery of lymphocytes (B and T cells)
• resolved granuloma with bacilli restricted to the centre

Question 6

Describe how a TB granuloma can become unresolved

Answer 6

• unbalanced state due to necrotic breakdown of the granuloma
• accumulation of caseum and cavitation of granulomas into necrotic material
• collapse of the granuloma allow TB infection to be released into the airway
• driven by both host and bacterial factors that induce cell-death

Question 7

How can TB infection be detected?

Answer 7

Tests of immunoreactivity to mycobacterial antigens can represent latent infection (HOWEVER, this can also occur after treatment/cleared infection)

Question 8

Describe the clinical presentation of TB

Answer 8

• Mainly pulmonary (cough +/- haemoptysis + SOB) and constitutional symptoms (eg. Fever, weight loss, fatigue, lymphadenopathy etc.)
• can cause wide variety of systemic symptoms

Question 9

Describe the symptoms of apical TB disease

Answer 9

• cough
• sputum
• haemoptysis
• fever
• weight loss
• night sweats

Question 10

How is latent TB diagnosed?

Answer 10

• mantoux (PDD tuberculin is injected into skin and positive = small hard red bump formation)
• interferon gamma release assays: (T-spot TB, quantiferon)
• T-spot TB: detects T cells that have been activated by MTB antigens
• quantiferon: detects IFN-gamma generation by patient’s T cell response to specific MTB antigens

Question 11

What are the 4 tubes used for in IGRA?

Answer 11

• purple (positive control): low response can indicate inability to generate IFN-gamma
• grey (negative control): adjusts for backgrouns IFN-gamma
• TB1: primarily detects CD4-T cell repsonse
• TB2: optimized for detection of CD4 and CD8 T cell responses

Question 12

Describe methods of diagnosing active TB

Answer 12

• AFB in respiratory or other sample (positive smear in microbiology, histopathology)
• positive MTB growth in cultures (solid LJ, liquid MGIT culture media)
• clinical/radiological diagnosis

Question 13

Describe treatment of latent TB

Answer 13

• isoniazid monotherapy for 6 months in adults and children in countries with high and low TB incidence (best)
• <15yo + high incidence = rifampicin + isoniazid for 3 months
• adults + children + high incidence = rifapentine + isoniazid weekly for 3 months
• Low incidence alternatives = 9 months isoniazid, 3-month weekly rifapentine + isoniazid, 3-4 months of isoniazid + rifampicin or just rifampicin

Question 14

Describe treatment of drug sensitive active TB

Answer 14

6 months
- 2 month intensive phase = rifampicin, isoniazid, ethambutol and pyrazinamide
- 4 month continuation phase = rifampicin and isoniazid

Question 15

What are the adverse events and interactions of TB treatment?

Answer 15

• rifampicin = enzyme inducer, flu symptoms, orange bodily secretions
• isoniazid = liver damage, lupus
• ethambutol = toxic optic neuropathy
• pyrazinamide = liver injury, raised lactate

Question 16

What is the greatest risks of non-adherence to full treatment of TB?

Answer 16

• generation of drug resistance
• not getting rid of all of infection

Question 17

What is the treatment for MDR TB?

Answer 17

• if resistant to rifampicin + isoniazid
• 18 month treatment of injectable drugs
• intensive phase (8-months) = pyrazinamide + fluoroquinolone + 2nd line injectable + eithionamide/prothionamide + cycloserine/p-aminosalicylic acid
• significant adverse effects
• risk of HIV and BBV transmission

Question 18

What is XDR TB and its treatment?

Answer 18

• additional MDR to include flouroquinolone + one of the injectables
• no standard treatment, consider surgery