THE CONTROL OF TUBERCULOSIS

1. THE CONTROL OF TUBERCULOSIS PRESENTER: Dr. PRACHETH.R. CHAIR-PERSON: Dr. MAYUR. S.S

2. Diagnosis • Chemotherapy • BCG vaccination • National Programme

3. TB Control • WHO: prevalence of natural infection in 0-14 years-1 % • Curative: Case finding and treatment • Preventive: BCG vaccination

4. Case finding • Case (Pulmonary), smear + TB: 1 initial sputum smear + for AFB or culture + for M.tuberculosis • Suspects: • all other sufferers- sputum negative but shadows in chest X-ray.

5. Contd… • Target group: • Persistent cough • Chest symptoms develop early • Most feasible group for case finding

6. Diagnostic tools

7. Direct Methods • Sputum Examination: • 2 samples • Early morning- secretions build up overnight • Day1- Sample 1- on the spot - sputum container given • Day 2- Sample 2- brings early morning sample

8. Contd… • Technique: • Inhale deeply 2-3 times • Cough deeply from chest • Open container, bring close to mouth, bring sputum out into it • No saliva/ nasal secretion given; close container • Open space • Empty bowel, bladder before starting

10. Advantages of sputum microscopy • More reliable • Simple • Minimal infrastructure • Inexpensive • Quick results • To monitor patient progress and declare the patient “ cured”.

11. ZeihlNeelsen Staining • Not reused- AFB may not be removed by cleaning • Smears prepared from thick purulent part of sputum • Dried, fixed • Covered with carbolfuschin • Heated gently by steaming: 5-7 minutes

12. Contd… • Wash slide with water • Decolorize with 25% sulphuric acid till no more stain comes off • 95% ethanol -2 minutes • Single step decolorization- acid alcohol (3%HCl in 95% ethanol)

13. Contd… • Wash • Counterstain – 0.1% Loeffler’smethylene blue or 1% picric acid or 0.2% malachite green- 1minute • AFB- bright red rods; blue/yellow /green background

15. Contd… • Disadvantages: • At least 10,000 bacilli per ml • False positive • Red stain- scratches on slide • Accidental transfer of AFBs • Environmental mycobacteria • Various acid fast particles (food particles, precipitates, saprophytes)

16. Contd…. • False negative • Problems in collecting • Inadequate sample • Inappropriate sputum container • Sputum stored too long before microscopy • Processing • faulty sampling of sputum, smear preparation, staining.

17. Misinterpreting sputum smears • Inadequate time in examining • Inadequate attention • Administrative errors • Misidentification of patients • Incorrect labeling of sample • Documentation errors

19. Sputum culture • Very sensitive • 30-50% smear negative cases diagnosed • 2 bottles : LJ medium/ the middlebrook 7H10 or 7H11 media • Incubate 37 degree C- 4days • Twice weekly thereafter • No growth after 8-12 weeks: negative • Smears from colonies developed- ZN stain, examined.

21. Mass miniature radiography • Not definite High cost • Misinterpretation of films • Very low yield of cases • Additional criteria- both smears negative • Frequent/severe hamoptysis- bronchiectasis/ aspergilloma • Complications in a breathless patient- pneumothorax, percardial/pleural effusion

23. Rapid Methods ( Microculture) • BACTEC: • Detect mycobacterium: 7-14 days • Radio labeled CO2 from growth of mycobacterium in selective liquid media using C14 labeled substrate • Extrapulmonary, smear negative TB • Expensive, not readily available

24. Other rapid methods • Micro colony detection on solid media • Microscopic observation of broth culture ( Liquid media) • Mycobacterium Growth Indicator Tube 960

25. Molecular Amplification methods-PCR • Amplify target nucleic acid enzymatically by PCR • Use nucleic acid probes for specific detection, identification • Detect positive signals from 1-10 bacilli in specimens tested, within a day

26. Phenotypic methods- Phage based assays • Mycobacteriophages infect live M. tuberculosis • After infection, bacilli detected by phage amplification

27. Indirect Methods • Antibody detection by TB- STAT-PAK • ELISA: • Specific Ab response using specific Ag (A 60) • Supportive; extrapulmonary TB • RFLP: • Southern blot + hybridization with specific DNA probes = characteristic band pattern (DNA finger prints)

28. Contd…. • Fast Plaque TB (FTB): • Site specific • Sputum, aspirates, pus, blood • Detect viable bacilli indicating active infection • Comparable with culture • Results: 48-72 hours • Sensitivity= 90% Specificity=100%

29. Contd… • QTB-G ( Quantiferon TB Gold): • Blood sample • Not affected by BCG vaccination • High sensitivity • Results within 3-5 days

30. Tuberculin Test • Principle: • Robert Koch- body reacts differently in first and subsequent infection • TB bacilli- thigh of guinea pig • No reaction: 7-10 days • Swelling- Ulcer: 3-4 weeks- glands of groin swollen

31. Contd… • After 6 weeks: again injected • Quick reaction – Swelling: 48 hours-Ulcer:3-4 days- Healed:4 weeks • Tuberculin: • PPD extract of dead tubercle bacilli • RT23 , Tween 80 • 1 TU= 1/50,000 mg protein part of bacilli • 1 ml= 0.002 mg protein part of bacilli

33. Mantoux test • 0.1 ml TU of PPD intradermally on flexor surface left forearm • Reading of result: • 72 hours ideal • Horizontal diameter of swelling (induration / hardness) ignoring redness

34. Contd… • Positive: • Induration> 10mm • Correlated: clinical features, diagnosis

35. Contd… • False positive: • Faulty technique • Degraded Tuberculin • Too deep injection • Infection-other mycobacterium • Repeated testing, particularly at same site- enhancement/booster effect

36. Contd… • Doubtful: 6-9 mm • False negatives: • Pre-allergic phase • High fever • Measles, chicken pox • Whooping cough • Malnutrition • HIV, AIDS • Anti-allergic drugs • Immuno suppressive drugs- steroids

37. Significance • If positive in children <5 years: further investigations needed to confirm diagnosis • If TB confirmed: full treatment given • Test positive, TB not confirmed: chemoprophylaxis • Negative Mantoux test: BCG given

38. Sensitivity tests • Many culture media – antitubercular drug innoculated • Minimum inhibitory concentration calculated from medium with least drug concentration that inhibits growth • Growth- bacilli resistant to drug

39. Diagnosis- Extrapulmonary Tuberculosis • Microscopy, culture: difficult to get conclusive result – bacilli few in number • CSF: spider web clot on standing • PCR, DNA probes • Bone marrow, liver biopsy- miliary TB • Pus from TB abscess-smear, culture

41. Chemotherapy • Every case of active TB • Cure- elimination of fast and slow multiplying bacilli • Elimination of bacilli from sputum • Easily available, free • Patient compliance

42. Anti- tuberculosis drugs • Highly effective • Free from side effects • Easy to administer • Cheap • Bactericidal • Bacteriostatic

43. Contd… • Bactericidal: • Rifampicin • INH • Streptomycin • Pyrazinamide • Bacteriostatic: • Ethambutol • Thioacetazone

44. First line drugs • Isoniazid (H) • Rifampicin (R) • Pyrazinamide (Z) • Ethambutol (E) • Streptomycin (S)

45. Isoniazid • Fast multiplying organisms rapidly killed • Extracellular and intracellular bacilli • Cheapest • Inhibit mycolic acid synthesis; inh A • INH resistance: mutation in catalaseperodixase enzyme

46. Contd… • Pharmacokinetics: • Completely absorbed orally • Liver- acetylation • Single dose: peak level 1-2 hours after dose • Interactions: • AlOH inhibits absorption • Inhibits phenytoin, carbamazepine, diazepam, warfarin metabolism

47. Contd… • Adverse effects: • Peripheral neuritis- pyridoxine • Hepatitis- older people

48. Rifampicin (RMP) • Derivative of rifamycin B- Streptomycesmediterranei • Active against persisters- better than INH • S.aureus, N. meningitidis, H.influenzae,E.coli • Inhibits DNA dependent RNA synthesis • Resistance due to repoB gene

49. Contd… • Well absorbed orally • Metabolised-liver: deacytalated metabolite • Absorption reduced by food • Increases metabolism of OCP , warfarin, corticosteroids,digoxin,

50. Contd… • Adverse effects: • Hepatitis • Respiratory syndrome: breathlessness • Purpura, haemolysis, renal failure • Cutaneous syndrome: flushing, pruritus +rash • Flu like syndrome: • Abdominal syndrome