Tuberculosis

Question 1

Who is TB most common in?

Answer 1

Tuberculosis is most common in people who are not born in the UK especially in ages between 20-44.

Question 2

What causes TB? Describe it’s characteristics?

Answer 2

Caused by mycobacterium tuberculosis complex. There are 7 closely related species: M. Tuberculosis, M.Bovis and M.Africanum.

Non-motile, rod, obligate aerobe, long chain fatty (mycolic) acids complex, waxes and glycolipids in cell wall. This give the cell it’s Structural rigidity and staining characteristics in the acid alcohol fast stain. Relatively slow growing compared to other bacteria. Generation time 15-20hours (S.Aureus and E.Coli is about 20 minutes).

Question 3

How is it transmitted?

Answer 3

Spread by respiratory droplets from coughing, sneezing, talking and laughing etc. Takes a large amount of contact time with someone else for you to become infected. Usually requires close contact and overcrowding. Air around people can remain infectious for 30 minutes.

Question 4

What is it’s parthenogenesis?

Answer 4

• Inhaled aerosols
• Engulfed by alveolar macrophages – Resists killing by macrophage and can replicate inside of them.
• Local Lymph nodes – can allow the spread of Tb to form disseminated TB
• Primary complex (Ghon’s focus which is the primary lesion + draining LN) - 5% progression to active disease which is known as Primary TB
• Most go to Initial containment of the infection
• Latent infection – live bacilli in the lung but they are not multiplying or damaging lung
• Heals/self-cure or reactivation - Post Primary TB.

Question 5

What is Primary TB?

Answer 5

Ghon Focus/Complex, limited by Cell mediated immune response. Usually asymptomatic, rare allergic reaction include EN. Occasional symptomatic – military/disseminated.

Question 6

What is Latent TB (post primary TB)

Answer 6

Reactivation or exogenous re-infection. >5 years after primary infection. 5-10% risk per lifetime. Clinical presentation – pulmonary or extra pulmonary.

Question 7

What risk factors are there for reactivation of TB?

Answer 7

• HIV
• Substance abuse
• Prolonged therapy with corticosteroids
• Immunosuppression therapy
• Anti TNF-alpha (i.e. antagonists)
• Haematological malignancy
• Severe kidney disease/haemodialysis
• Diabetes Mellitus
• Silicosis (Lung fibrosis due to silica inhalation)
• Low body weight,

Question 8

How does TB affect people differently with increasingly poor immune systems?

Answer 8

• Healthy contact – LTBI (latent TB infection)
• Lymph node
• Localised Extra pulmonary
• Pulmonary localised
• Pulmonary widespread
• Meningeal
• Miliary TB – TB present throughout the body carried via blood stream

Question 9

Describe the common histological sign seen with TB?

Answer 9

Tuberculous Granuloma. Caesous necrosis in the centres looks like liquefied cheesy material of dead and dying bacteria and inflammatory cells. Surrounding the edge are Giant cell Langerhans type surrounding the centre. Epithelioid histiocytes (modified immobile macrophages (activated)) and Lymphocytes

Question 10

Who should you suspect of TB?

Answer 10

Who to suspect: Non UK born, HIV, Other immunocompromised patients, Homeless, Drug users, prisons, Close contacts and young adults

Question 11

What should you discern from a History?

Answer 11

Ethnicity, Recent travel, Contacts with TB, BCG vaccination and Specific clinical features such as Fever, weight loss, malaise and anorexia.

Question 12

What are the common symptoms associated with TB?

Answer 12

Fever, Night sweats (evening pyrexia), Weight loss and anorexia, Tiredness and malaise, Cough, Haemoptysis occasionally, Breathlessness if pleural effusion, Often no chest signs despite abnormal CXR and May be crackles in affected area. In extensive disease – signs of cavitation and fibrosis

Question 13

What investigations should be done to assist diagnosis of TB?

Answer 13

CXR, Sputum – 3 early morning samples minimum volume 5ml – induced sputum (vasodilators and physiotherapy or Bronchoscopy for patients who still can’t produce sputum).

Radiology
Apex of the lung often involved, ill-defined patchy consolidation which usually contains cavitations within the consolidation. This occurs because the macrophages infected with TB put out lots of cytokines causing wide spread damage to the organ.

Question 14

How can you confirm TB infections and how effective is this?

Answer 14

Only 25 % of people with TB will have a lab confirmed diagnosis. Done with an acid-fast stain and auramine stain. Takes 1-3 weeks with modern automated systems. Doing a culture is the gold standard for diagnosis but it takes too long.

Can do PCR looking for DNA of TB – this isn’t widely available and is also expensive

Question 15

What is the Tuberculin Sensitivity Test?

Answer 15

Tuberculin Sensitivity Test – utilises antigen called Purified Peptide Derivative – injected intradermally and the reaction to this is measured by colour. Causes an exaggerated sensitivity reaction. Measure the induration i.e. the centre bit 2-3 days later. May have false positives if you have had the BCG or false negatives with HIV or some drugs and the size is subject to interpretation

Question 16

What are IGRAs? (Interferon Gamma releasing Assays?

Answer 16

Detection of antigens specific IFN gamma production. If you have desensitised T cells and challenge them in the lab, these will become activated. No cross reaction with BCG but you can’t distinguish latent and active TB.

Question 17

What drugs are there than can target TB?

Answer 17

Rifampicin – raised transaminases and induces cytochrome P450 – orange secretions
Isoniazid – Peripheral neuropathy, hepatotoxicity
Pyrazinamide – Hepatotoxicity
Ethambutol – Visual disturbances

Question 18

What other treatments are there for TB?

Answer 18

Vitamin D supplements should be considered and the final option is surgery.

Must treat early and with adequate medication i.e. multiple at the same time due to resistance and in combination due to resistance. Treat for a long time due to TB long generation period. This and the side effects creates low adherence so we have directly observed therapy (DOT) and Video observed therapy (VOT) and increase compliance.

Question 19

Describe the common resistance to TB?

Answer 19

Single drug resistance
Multi drug resistance TB (MDR) – resistant to rifampicin and isoniazid
Extremely drug resistant TB (XDR) – also resistant to fluoroquinolones and 1+ injectable

Question 20

What is Miliary TB?

Answer 20

Bacilli spreading through the blood stream causing widespread infection. This can occur either during primary infection or during reactivation. Lungs are always involved but few respiratory symptoms. Multiple organs will become involved and symptoms will reflect this. Headaches suggest meningeal involvement, ascites may be present and retinal involvement in children.

Question 21

What are the common extra pulmonary TB?

Answer 21

Pleural TB – occurs in wo ways either due to hypersensitivity response in primary infection or by TB empyema where the Tb ruptures the cavity. It is more common in Males.

Lymph Node TB – more common in children, women and Asian. Often painless and occurs commonly at the neck.

Gastrointestinal TB – occurs by swallowing of tubercles

Genitourinary – slow progression to renal disease and subsequent spreading to lower UTI

Osteo-articular TB – spread haematogenously then burrows into the bone. There are two types
• Tuberculous Spondylitis (Pott’s disease) – this is most common and begins in the subchondral bone then spreads to the vertebral bodies following up the longitudinal ligaments. Mainly occurs in the thoracic and lumbar spine but can reach cervical.
• Poncet’s disease – aseptic polyarthritis in the knees, ankles and elbows.

Tuberculous meningitis – chronic headache, fevers, CSF (cerebral spinal fluid) has markedly raised proteins and lymphocytes.

Question 22

How do we prevent the spread of TB?

Answer 22

Must notify so that all potential contacts that could be cases can be tested. Notification triggers contact tracing procedures and active case finding of symptomatic patients.

Prevention of transmission – personal protective equipment and negative pressure isolation.

BCG vaccine