Tuberculosis

Question 1

What are key features of tuberculosis?

Answer 1

• Caused by Mycobacterium tuberculosis
• Most commonly affects lung
• Can be primary or secondary

Question 2

What is primary TB?

Answer 2

• Non-immune host who is exposed to M. tuberculosis may develop primary infection of lungs
• Small lung lesion known as ‘Ghon focus’ develops
• Ghon focus → tubercle-laden macrophages
• Combo of Ghon focus + hilar lymph nodes = Ghon complex
• In immunocompetent people → initially lesion heals by fibrosis
• Immunocompromised → may develop disseminated disease (miliary TB)

Question 3

What is secondary (post-primary) TB?

Answer 3

• If host becomes immunocompromised, initial infection reactivated
• Reactivation occurs in apex of lungs + may spread locally or to distant sites
• Causes of immunocompromise → drugs (steroids), HIV, malnutrition
• Lungs remain most common site for 2^o TB

Question 4

What are extra-pulmonary sites for secondary TB infection?

Answer 4

• CNS → tuberculosis meningitis (most serious complication)
• Vertebral bodies → Pott’s disease
• Cervical lymph nodes → scrofuloderma
• Renal
• GI Tract

Question 5

What is the pathology of tuberculosis?

Answer 5

• Mycobacterium tuberculosis
• Macrophages often migrate to regional lymph nodes
• Lung lesion + affected lymph nodes = Ghon complex
• Leads to formation of granuloma (collection of epithelioid histiocytes)
• Presence of caseous necrosis in centre
• Inflammatory response mediated by type 4 hypersensitivity reaction
• In healthy individuals, disease may be contained
• In immunocompromised → disseminated (miliary TB) may occur

Question 6

How is tuberculosis screened for?

Answer 6

• Mantoux test screens for latent TB
• Interferon-gamma blood test also introduced
• Mantoux test → injected intradermally, result read 2-3d later
• False negatives → miliary TB, sarcoidosis, HIV, lymphoma, <6months age
• Heaf test prev used in UK but since discontinued, was read 3-10d later

Question 7

What does CXR show for active tuberculosis?

Answer 7

• Classical finding of reactivated TB → upper lobe cavitation
• Bilateral hilar lymphadenopathy

Question 8

What is the investigation of choice for TB?

Answer 8

• Sputum smear
• 3 specimens needed
• Rapid + inexpensive test
• Stained for presence of acid-fast bacilli → Ziehl-Neelsen stain
• All mycobacteria will stain positive
• Sensitivity 50-80%, reduced in individuals w/ HIV to around 20-30%

Question 9

What is the gold standard investigation for TB?

Answer 9

• Sputum culture
• More sensitive than sputum spear + NAAT
• Can assess drug sensitivities
• Can take 1-3 weeks if using liquid media, longer if solid media

Question 10

What is NAAT?

Answer 10

• Another investigation for TB
• Nucleic acid amplification tests (NAAT)
• Allows rapid diagnosis within 24-48hrs
• More sensitive than smear but less sensitive than culture

Question 11

What are risk factors for developing active tuberculosis?

Answer 11

• Silicosis
• Chronic renal failure
• HIV positive
• Solid organ transplantation w/ immunosuppression
• IV drug use
• Haem malignancy
• Anti-TNF treatment
• Prev gastectomy

Question 12

What is the treatment for latent tuberculosis?

Answer 12

Two choices from NICE:

• 3 months isoniazid (w/ pyridoxine) + rifampicin, or
• 6 months of isoniazid (w/ pyridoxine)

NICE Reasoning → Base the choice of regimen on the person’s clinical circumstances. Offer:

• 3 months isoniazid (w/ pyridoxine) + rifampacin to < 35yrs if hepatotoxicity is a concern after an assessment of both LFTs and risk factors
• 6 months of isoniazid (w/ pyridoxine) if interactions w/ rifamycins are a concern, if example, in ppl w/ HIV or transplant pts

Question 13

What is the standard therapy for treating active TB?

Answer 13

• Initially: first 2 months → rifampicin, isoniazid, pyrazinamide + ethambutol
• Continuation: next 4 months → rifampicin + isoniazid

Question 14

Which groups is direct observed therapy (3 times a week dosing regimen) indicated in?

Answer 14

• Homeless people w/ active TB
• Pts who are likely to have poor concordance
• All prisoners w/ active or latent TB

Question 15

What are TB drug side-effects?

Answer 15

• Rifampicin → red-orange secretions, hepatitis, flu-like symptoms
• Isoniazid → peripheral neuropathy (prevent w/ pyridoxine/Vit B6), agranulocytosis, hepatitis
• Pyrazinamide → hyperuricaemia, arthralgia, myalgia, hepatitis
• Ethambutol → colour blindness, optic neuritis

Question 16

What are features of the vaccine for TB?

Answer 16

• BCG vaccine, interdermal
• Given to high-risk infants
• Live attenuated Mycobacterium bovis
• CIs → prev BCG, past hx of TB, HIV, preg, positive tuberculin test
• Before administration needs to be given tuberculin skin test