Worlds leading cause of death from a single infectious disease, with two million deaths in 2000.
This is a result of:
- Inadequate programmes for disease control with poorly supervised treatment (no DOTs)
- Multiple drug resistance (MDR/XDR-TB): 6-7% is MDR, 25% of which is XDR. MDR-TB is resistant to R&I. XDR-TB has 98% mortality in 1/12.
- Co-infection with HIV (70% of Africa co-infected).
- A rapid rise in the world’s population of young adults = the age group with the highest mortality from TB
- Overcrowding and poor nutrition
In the UK:
- ~8000 cases/y
- 39% cases from London
- 72% cases of immigrant status.
- Primary = first infection
- Post-primary – reactivation of old primary.
Presentation: apical lung cavitation
Primary TB p/c: 30-34yo, asymptomatic, vague cough, wheeze, small pleural effusion, erythema nodosum. Occasionally persistant collapse can give rise to bronchiectasis in the middle lobe = Brock’s syndrome.
Post-primary tuberculosis p/c: 70-74yo, fatigue, malaise, anorexia, weight loss, chest ache, pleural effusion/pneumonia, pleuritic pain, dyspnoea, haemoptysis, fever,
RFs for TB: silicosis (x30 risk), CRF (x10-25), DM (x2-4), low body weight, IVDU…
- Chest xray and CT scan – visualise lesion / cavitation
- o Sputum is stained with Ziehl-Neelsen stain ( CANNOT be Gram stained due to waxy capsule) for acid and alcohol-fast bacilli (ZNS for AAFB).
- o Sputum is cultured on Ogana or Lowenstein-Jensen medium for 4-8 weeks.
- Fibreoptic bronchoscopy
- o With washing of affected lobes if no sputum is available – or broncho-alveolar lavage (BAL)
Mycobacterium tuberculosis (MTB): small, aerobic, non-motile, high lipid content, Gram +ve (but cannot be stained due to capsule), ZNS will show AAFB
Mycobacterium complex: M.bovis, M.africanuum, M.canetti, M.microti
The first infection with M.tuberculosis = Primary Tuberculosis.
- Usually subpleural, often in mid to upper zones = Ghon focus
- Within a few hours of reaching the lung, tubercle bacilli reach the lymph nodes and go into blood.
- Initial reaction is an exudative response and infiltration with neutrophil granulocytes.
- These are rapidly replaced by macrophages that ingest the bacilli.
- Interact with T lymphocytes
- Development of cellular immunity by 3-8 weeks after initial infection.
- Also get delayed hypersensitivity reaction which results in tissue necrosis and results in the pathology of tuberculosis.
- Development of granulomatous lesions
- Central area of necrotic caseation material, surrounded by epithelioid cells and Langhan’s giant cells with multiple nuclei. (Both cells derived from macrophages).
- Heal and become calcified.
- 20% contain tubercle bacilli
Adult post-primary tuberculosis: Reactivation leads to post-primary tuberculosis with cavitation (second lesion = Assman focus). Gradual onset of symptoms over weeks and months
Miliary tuberculosis can occur within a year of the primary infection.
- Result of acute dissemination of tubercle bacilli via the blood stream.
- Difficult diagnosis especially in older people.
- Fatal without treatment – aggressive sepsis!
- Occasionally presents as tuberculous meningitis.
- Mantoux test is usually positive
- o Negative in very severe disease.
- Involve LNs, bone (Pott’s disease of the spine), joints, soft tissue, GU.
- More common in the immunosuppressed.
- Induces liver enzymes which are elevated in serum of patients.
- Stop drug if bilirubin is elevated or liver transferases are >3x elevated.
- Stains body secretions orange.
- Oral contraceptive is not effective – use alternative form of contraception.
- Few unwanted side effects
- May produce polyneuropathy in high doses
- o Prescribe pyridoxine (Vit B6) to prevent this
- Hepatic toxicity
- Reduces the renal excretion of urate and may precipitate gout
- Dose-related optic retrobulbar neuritis
- o Presents with colour blindness for green, reduction in visual acuity and central scotoma.
- o Usually reverses when drug stopped.
Regime: 1st 2/12 RIPE, further 4/12 just R&I. to be conducted under DOT to maximise compliance.