2 TUBERCULOSIS 2.pptx ( introduction to management)
- 1. Tuberculosis Col G Sandala Bsc Cli Med, BA (AE), Dip Th, Cert Mil Chreso University 1 Makeni Camp
- 2. Objectives • Definition • Aetiology • Pathogenesis and pathology • Clinical presentation • Investigations • Types of TB • Treatment regimens • Relationship to HIV/AIDS 2 Makeni Camp
- 3. Definition • A chronic infectious disease caused by mycobacteria (commonly by Mycobacterium tuberculosis) • It may affect any organ or tissue but commonly affects the lungs 3 Makeni Camp
- 4. Aetiology • Besides Mycobacterium tuberculosis, other types are: M. Leprae M. bovis M. avium M. kansasii M. intracellulare 4 Makeni Camp
- 5. Mode of transmission • Airborne (infectious droplets). • The source of infection is a person with pulmonary-TB who is coughing and is sputum smear-positive • Or drinks infected cow’s milk in case of bovis. 5 Makeni Camp
- 6. Note • Transmission generally occurs indoors. • Two factors determine an individual’s risk of exposure: The concentration of the droplet in air. The length of time somebody breathes that air. 6 Makeni Camp
- 7. Pathogenesis • TB may involve any organ but the lungs are the usual site of primary lesion. • TB bacilli in the lungs requires oxygen for growth • The inhaled bacilli implants in the distal airspaces of the upper lobe or of the lower lobe 7 Makeni Camp
- 8. Cont’d • TB bacilli lodge within the alveolus → rapidly phagocytized, mostly by alveolar macrophages. • Because TB bacilli are resistant to destruction, they multiply within macrophages • Bacilli have naturally slow multiplication rate, hence appearance of signs and symptoms may require several weeks. 8 Makeni Camp
- 9. Cont’d • When the number of TB bacilli becomes significant, inflammation ensues forming a ‘Primary’ or ‘Ghon’s’ focus. Usually the primary focus heals completely. • The center undergoes caseous necrosis • If not: dissemination of TB bacilli from the focus may follow, probably within hours • Dissemination is primarily by lymphatics 9 Makeni Camp
- 10. Primary Pulmonary TB The gray-white parenchymal focus is under the pleura under the lower part of the upper lobe. Hilar lymph nodes with caseation are seen on the left 10 Makeni Camp
- 11. Cont’d • Involvement of the Primary focus, lymphangitis and the hilar lymphnodes is called Primary complex. • Cellular immunity develops three to eight weeks after the initial infection • Spill over of TB bacilli from lymphatics into blood stream may occur leading to seeding of bacilli to other organs → milliary. 11 Makeni Camp
- 12. Cont’d • Primary complex - caseated areas - heals in the majority, within few weeks and undergo calcification • In some cases: seeding of bacilli advances → wide spread disease → death if no treatment is given. • NB: at least 20% of calcified primary lesions contain TB bacilli, initially lying dormant but can reactivate 12 Makeni Camp
- 13. Pathogenesis Ghon Focus – lungs, regional lymph nodes Mycobacterium tuberculosis 13 Makeni Camp
- 14. Pathogenesis Ghon Focus – lungs, regional lymph nodes) Immune response Mycobacterium tuberculosis Successful Fails Latent TB Active TB 14 Makeni Camp
- 15. Clinical feature • Haemoptysis. • Chest pain. • Difficult in breathing. • Cough of 2 weeks or more 15 Makeni Camp
- 16. Cont’d Constitutional symptoms: • Evening fever. • Night sweats. • Tiredness/weakness. • Loss of appetite. • Weight loss 16 Makeni Camp
- 17. Cont’d • Respiratory distress (Respiratory rate of more than 30 breathes per minute is significant in adults). • Lymphadenopathy: • Anterior cervical and the axillae. • Generalized lymphadenopathy is more likely to be HIV related. 17 Makeni Camp
- 18. Cont’d • Varies; crepitations, bronchial breath sounds reduced air entry. 18 Makeni Camp
- 19. Investigations Chest x-ray Gen-Xpert (Diagnostic and MDR) Sputum smear FBC ESR Mantoux Test 19 Makeni Camp
- 20. CHEST XRAY TB Right apical consolidation 20 Makeni Camp
- 21. The Mantoux Test • Infection with M. Tuberculosis → delayed hypersensitivity which can be detected by the tuberculin test (Mantoux) • A positive tuberculin test does not differentiate infection and disease but signifies cell-mediated hypersensitivity to tubercular antigens • Induces an induration ≥ 5mm 21 Makeni Camp
- 22. The Mantoux Test • A false negative result may occur due to immunosuppression and overwhelming active TB • False positives occur in atypical mycobacteria infections 22 Makeni Camp
- 23. Differential diagnoses of chest x-ray findings Chest x-ray findings Differential diagnoses Pleural effusion. •Malignancy: Often causes blood stained effusion. • Pneumonia. •Heart failure. •Renal failure. •Nephrotic syndrome. 23 Makeni Camp
- 24. Complications of PTB • Massive haemoptysis. • Cor pulmonale. • Lung fibrosis • Lung or pleural calcification. • Obstructive airways disease. • Bronchopleural fistula. • Pneumothorax. 24 Makeni Camp
- 25. Cont’d • Pleurisy with effusion • Miliary tb • Meningitis • Bone and joint disease 25 Makeni Camp
- 26. Miliary-Tuberculosis • Miliary-TB results from widespread blood- borne dissemination of TB bacilli. • This is either the consequence of the recent primary infection or the erosion of a tuberculous lesion into a blood vessel. 26 Makeni Camp
- 27. Miliary TB of the spleen. Section shows numerous gray-white granulomas 27 Makeni Camp
- 28. Other forms of extrapulmonary tuberculosis Site of the disease Clinical features Diagnosis TB-spine (Pott’s disease) •Backache. •Gibbus deformity. •Spinal cord compression. •Paraplegia. X-ray of the spine shows erosion of anterior edges of the superior and inferior borders of adjacent vertebral bodies with narrowing of the intervertebral disc space. 28 Makeni Camp
- 29. Other forms of extrapulmonary tuberculosis Site of the disease Clinical features Diagnosis TB of the bone Chronic Osteomyelitis. Tissue biopsy. Gastrointestinal-TB Right iliac fossae mass. Chronic diarrhoea. Subacute intestinal obstruction. Barium enema of the small and large bowel. Colonoscopy Renal and urinary tract TB •Urinary frequency. •Dysuria. •Haematuria. •Loin pain or swelling. •Sterile pyuria urine culture. •Intravenous pyelogram. 29 Makeni Camp
- 30. First-line anti-TB drugs Bactericidal drugs: Isoniazid: (H) Highly potent Anti-TB drug most effective against the metabolically active, continuously growing bacilli. Mode of action: Inhibitor of mycobacterial cell wall synthesis. Common side effects: Peripheral neuropathy due to pyridoxine deficiency. Drug-induced hepatitis. 30 Makeni Camp
- 31. Bactericidal drugs: Rifampicin: (R) Highly potent Anti-TB drug that can kill the semi-dormant bacilli (persisters) which Isoniazid cannot. Mode of action: Inhibitor of DNA transcription. Common side effects: Anorexia, nausea, vomiting and abdominal pain. Drug-induced hepatitis. Reduced effectiveness of oral contraceptive 31 Makeni Camp
- 32. Bactericidal drugs: Pyrazinamide: (Z) Anti-TB drug with low potency that can kill bacilli in an acid environment inside cells e.g. macrophages. Mode of action: Unknown. Common side effects: Joint pain. Drug-induced hepatitis. 32 Makeni Camp
- 33. Bacteriostatic drug: Ethambutol: (E) Anti-TB drug with low potency. Mode of action: Inhibits mycobacterial cell wall synthesis. Common side effects: Optic neuritis 33 Makeni Camp
- 34. Bacteriostatic drug: Thiacetazone: (T) Anti-TB drug with low potency. It is contraindicated in HIV infected patients because of high risk of severe and potentially fatal skin reaction. 34 Makeni Camp
- 35. Bactericidal drugs: Streptomycin (S): Phased out How are the four drugs above given and the periods covered? 35 Makeni Camp
- 37. Introduction • MDR mycobacterium tuberculosis is a major and increasing problem in TB treatment and control • Resistance to both isoniazid (INH) and rifampicin (RIF) • INH and RIF are the two most potent antituberculous drugs. they kill more than 99% of TB bacilli within 2 months of initiation of therapy • Pyrazinamide (PZ) has a high sterilizing effect acting on semi dormant bacilli 37 Makeni Camp
- 38. Patients at risk of developing MDR TB • Patients who remain or turn +ve after 4 months of ATT • Patients previously treated for TB • Contact with known MDR Patients • Hospital and health care workers • HIV Patients Prisoners 38 Makeni Camp
- 39. Types of resistance Primary: • infection by mycobacterial strain that is already resistant to INH and RF Acquired: • Development of Resistance in a bacilli that was previously sensitive to the regular Rx 39 Makeni Camp
- 40. Mechanism of resistance • Specialized cell wall has significantly reduced permeability to many compounds • Modifications by mutations in the drug target genes leading to an altered target • Change in the titration (dosage) of the drugs through overproduction of the target 40 Makeni Camp
- 41. Resistance contd • MDR TB reflects the stepwise accumulation of individual mutations in several independent genes • Mutations are generally chromosomal 41 Makeni Camp
- 42. WHO Categories for MDR/XDR TB treatment 42 Makeni Camp
- 43. 43 Makeni Camp
Editor's Notes
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