Tuberculosis (TB)

Epidemiology:

• TB is the world’s leading cause of death from a single infectious disease
• 2,000,000 deaths in 1990
• This is the result of:
• Inadequate programmes for disease control
• Drug resistance
• Co-infection with HIV

• In the UK, there are 7,000 new cases per year
• In the UK, the highest risk groups are immigrants from the Asian subcontinent and the West Indies
• TB is a notifiable disease

Pathology:

• The initial infection with M.tuberculosis is known as primary tuberculosis
• It is usually subpleural, often in the mid to upper zones
• Within an hour of reaching the lung, tubercle bacilli reach the draining lymph nodes at the hilum of the lung and a few escape into the bloodstream
• The initial reaction comprises:
• Exudation
• Infiltration with neutrophil granulocytes (these are rapidly replaced by macrophages which ingest the bacilli)

• Granulomatous lesions consist of a central area of necrotic material of a cheesy nature (called caseation) surrounded by epithelioid cells and Langerhan’s giant cells
• Subsequently, the caseated areas heal and many become calcified
• It is known that at least 20% of these calcified primary lesions contain tubercle bacilli, initially lying dormant but capable of being reactivated by depression of the hosts immune system
• Reactivation leads to typical post-primary pulmonary TB with cavitation, usually in the apex or upper zones of the lung
• Post-primary TB refers to all forms of TB that occur after the first few weeks of the primary infection when immunity to the mycobacterium has developed

Clinical features of primary TB:

• Asymptomatic in the majority of individuals
• Cough
• Wheeze
• Small, transient, pleural effusion
• Erythema nodosum

What can cause reactivation?

• Increasing age
• Diabetes mellitus
• Malnutrition
• Immunosuppression
• AIDS
• Lymphoma

Miliary TB:

• Is the result of acute diffuse dissemination of tubercle bacilli via the bloodstream
• Is universally fatal unless treated
• It may present in an entirely non-specific manner with a gradual onset of:
• Vague ill-health
• Weight loss
• Fever

• Occasionally it presents as tuberculosis meningitis
• Positive Mantoux test
• Transbronchial biopsies are frequently positive before any abnormality is visible on the CXR

Adult post-primary TB:

• Typically, there is a gradual onset of symptoms over weeks or months:
• Tiredness
• Malaise
• Weight loss
• Fever
• Cough
• Sputum in TB may be:
• Mucoid
• Purulent
• Blood-stained

• A pleural effusion or pneumonia can be the presenting feature of TB

On examination:

• Very few signs
• Finger clubbing (if disease is advanced and associated with considerable production of purulent sputum)

Investigating adult post-primary TB:

CXR:

• An abnormal CXR is often found with no symptoms, but the reverse is extremely rare (pulmonary TB is unlikely in the absence of any radiographic abnormality)
• Typically shows:
• Patchy or nodular shadows in the upper zones
• Loss of volume
• Fibrosis (with or without cavitation)
• Calcification may be present

Diagnosis:

The diagnosis is made on the basis of the following investigations:

Imaging:

• CXR
• CT

Staining:

• The sputum is stained with Ziehl-Nielsen (ZN) stain for acid-fast and alcohol-fast bacilli (AAFB)

Culture:

• The sputum is cultured for 4-8 weeks
• Cultures to determine the sensitivity of the bacillus to antibiotics take a further 3-4 weeks

Fibre-optic bronchoscopy with washings from the affected lobe(s):

• Useful if no sputum is available

Biopsies of the:

• Pleura
• Lymph nodes
• Solid lesions within the lung (tuberculomas)

Treatment:

Directly observed therapy (DOT):

• In order to improve compliance, special clinics are used to supervise treatment regimens directly
• Incentives to attend (e.g. free meals) may be helpful

Six-month regimen:

• This is standard practice for patients with pulmonary and lymph node disease
• Daily administration of:
• Rifampicin 600mg, and
• Isoniazid 300mg
• Pyrazinamide 1.5-2g (for the first two months only)

• These are given as combination tablets and are taken 30 minutes before breakfast (since the absorption of rifampicin is influenced by food)

Longer regimens:

• Treatment of bone TB should be continued for a total of 9 months
• Tuberculosis meningitis should be treated for 1 year
• The drugs are the same as for pulmonary TB

Unwanted effects of drug treatment:

Rifampicin:

• Induces liver enzymes
• Drug should only be stopped if the serum bilirubin becomes elevated (which is extremely rare)
• Stains body secretions pink (urine, tears, sweat
• Due to the induction of liver enzymes, other drugs will be affected (e.g. the OCP is ineffective whilst taking rifampicin)

Isoniazid:

• Very few unwanted effects
• Skin rash, fever and hepatitis occur in <1% of patients
• If hepatitis occurs, isoniazid must be stopped
• May produce a polyneuropathy in high doses (therefore, give pyridoxine 10mg daily to prevent this)

Pyrazinamide:

• The main unwanted side-effect of this drug is severe hepatic toxicity, although it is not very common
• Gout may occur owing to hyperuricaemia