Tuberculosis basics


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Tuberculosis basics

  1. 1. Tuberculosis basics Dr.T.V.Rao MD Dr.T.V.Rao MD 1
  2. 2. HISTORY of Tuberculosis Tuberculosis Is anAncient Disease Spinal Tuberculosisin Egyptian Mummies History dates to1550 – 1080 BC Identified byPCR Dr.T.V.Rao MD 2
  3. 3. Robert Koch Discoverer ofMycobacterium Tuberculosis Dr.T.V.Rao MD 3
  4. 4. What are Mycobacteria?• Obligate aerobes growing most successfully in tissues with a high oxygen content, such as the lungs.• Facultative intracellular pathogens usually infecting mononuclear phagocytes (e.g. macrophages). Dr.T.V.Rao MD 4
  5. 5. Classification of Mycobacteria1. Tubercle bacilli 4. Atypical Mycobacteria a) Human – MTB (Runyon Groups) b) Bovine – M. bovis a) Photochromogens c) Murine – M. microti b) Scotochromogens d) Avian – M. avium c) Nonphotochromogens e) Cold blooded – M. d) Rapid growers marinum 5. Johne’s bacillus2. Lepra bacilli M. paratuberculosis a) Human – M. leprae b) Rat – M. leprae murium 6. Saprophytic mycobacteria a) M. butyricum3. Mycobacteria causing skin b) M. phlei ulcers c) M. stercoralis a) M. ulcerans d) M. smegmatis b) M. belnei e) Others Dr.T.V.Rao MD 5
  6. 6. Mycobacterium differ from other routinely isolated Bacteria• Slow-growing with a generation time of 12 to 18 hours (c.f. 20-30 minutes for Escherichia coli).• Hydrophobic with a high lipid content in the cell wall. Because the cells are hydrophobic and tend to clump together, they are impermeable to the usual stains, e.g. Grams stain Dr.T.V.Rao MD 6
  7. 7. Acid fast bacilli• Known as “Acid-fast bacilli" because of their lipid-rich cell walls, which are relatively impermeable to various basic dyes unless the dyes are combined with phenol. Dr.T.V.Rao MD 7
  8. 8. How they are Acid fast• Once stained, the cells resist decolourization with acidified organic solvents and are therefore called "acid-fast". (Other bacteria which also contain mycolic acids, such as Nocardia, can also exhibit this feature.) Dr.T.V.Rao MD 8
  9. 9. Mycobacterium tuberculosis complex• Includes Human and Bovine mycobacterium• M .Africanism Tropical Africa• M.microti do not cause human infections but in small mammals Dr.T.V.Rao MD 9
  10. 10. M.bovis• Primarily infection among the cattle• M.bovis infects Tonsils, Cervical nodes, can produce Scrofula.• Enter through Intestines – infects the Ileocecal region. Dr.T.V.Rao MD 10
  11. 11. What are atypical Mycobacterium• Infects birds, cold blooded animals worm blooded animals• Present in environment• Opportunistic pathogens• Others – Saprophytic bacteria M butryicum present in butter M.phlei M smegmatis – present in Smegma Dr.T.V.Rao MD 11
  12. 12. Atypical Mycobacterium• 1 Photochromogens• 2 Scotochromogens• 3 Non Photochromogens• 4 Rapid growers Dr.T.V.Rao MD 12
  13. 13. MOST IMPORTANT AMONG INFECTIOUS DISEASES• Tuberculosis (TB) is the leading cause of death in the world from a bacterial infectious disease. The disease affects 1.8 billion people/year which is equal to one- third of the entire world population. Dr.T.V.Rao MD 13
  14. 14. Poverty and Crowded living spreads Tuberculosis Dr.T.V.Rao MD 14
  15. 15. Tuberculosis infects Famous people too Dr.T.V.Rao MD 15
  16. 16. What are Mycobacteria?• Obligate aerobes growing most successfully in tissues with a high oxygen content, such as the lungs.• Facultative intracellular pathogens usually infecting mononuclear phagocytes (e.g. macrophages). Dr.T.V.Rao MD 16
  17. 17. General characters of the genus• Slender rods • Aerobic, Non- motile, Non-sporing, Non-• Resist staining but capsulated. once stained, resist • Growth generally slow decolonization by • Genus includes dilute mineral acids; – Obligate parasites hence called ACID – Opportunist pathogens – Saprophytes FAST BACILLI (AFB) Dr.T.V.Rao MD 17
  18. 18. Morphology of Mycobacterium tuberculosis• Straight, slightly curved Rod shaped 3 x 0.3microns• May be single, in pairs or in small clumps• On conditions in growth appears as filamentous, club shaped, or in Branched forms. Dr.T.V.Rao MD 18
  19. 19. ACID FAST BACILLI• Known as “Acid-fast bacilli" because of their lipid-rich cell walls, which are relatively impermeable to various basic dyes unless the dyes are combined with phenol. Dr.T.V.Rao MD 19
  20. 20. Important Mycobacterium• Mycobacterium tuberculosis, along with M. bovis, M. africanum, and M. microti all cause the disease known as tuberculosis (TB) and are members of the tuberculosis species complex. Each member of the TB complex is pathogenic, but M. tuberculosis is pathogenic for humans while M. bovis is usually pathogenic for animals Dr.T.V.Rao MD 20
  21. 21. Avian Tuberculosis• Transmitted by ingestion and inhalation of aerosolized infectious organisms from feces.• Oral ingestion of food and water contaminated with feces is the most common method of infection.• Once ingested, the organism spreads throughout the birds body and is shed in large numbers in the feces.• If the bacterium is inhaled, pulmonary lesions and skin invasions may occur• transmission of avian TB is from bird to human not from human to human. Dr.T.V.Rao MD 21
  22. 22. Acid Fast Bacilli seen in a specimen of Sputum Dr.T.V.Rao MD 22
  23. 23. Acid fast Bacilli seen as in Florescent Microscope• After staining with Ziehl Neelsen method or Fluorescent method ( Auramine or Rhodamine they resist decolonization by 20% Sulphuric acid and absolute alcohol for 10 mt,• So called as Acid and Alchool fast. Dr.T.V.Rao MD 23
  24. 24. Why they are Acid Fast • The character of Acid fastness is due to presence of Unsapnofiable wax ( My colic acid and semi permeable membrane around the cell) Dr.T.V.Rao MD 24
  25. 25. MTB : Cultural characters• Grow slowly. • MTB grows more Generation time luxuriantly (eugonic) 14-15 hrs than M. bovis (dysgonic).• Colonies appear • Addition of 0.5% after 2 weeks or at Glycerol supports 6-8 weeks growth of human• MTB - Obligate strains. No effect or aerobe inhibitory effect on bovine strains. Dr.T.V.Rao MD 25
  26. 26. Culturing Acid Fast Bacilli• Slow to grow ,• Generation time is 14 – 15 hours• > 2 weeks minimal required period• Grows at 370c do not grow below 250c• Ph between 6.4 to 7.0 Dr.T.V.Rao MD 26
  27. 27. Eight Week Growth of Mycobacteriumtuberculosis on Lowenstein-Jensen Agar Dr.T.V.Rao MD 27
  28. 28. Nature of Media Used• Helps the growth needs• Solid Medium is commonly used• Lowenstein Jensen’s medium• Petrangini• Middle brook medium Dr.T.V.Rao MD 28
  29. 29. Lowenstein Jensen’s Medium• Contain coagulated egg• Mineral salt solution• Asparagines• Malachite green• Agar Dr.T.V.Rao MD 29
  30. 30. Other Medium•Middle brook•Sulas medium•But not routinely used Dr.T.V.Rao MD 30
  31. 31. Nature of Growth Characters• M tuberculosis is obligate aerobe• M.bovis Microaerophilic• M.tuberculosis growth luxierently• M.tuberculosis eugonic• M bovis is dysgonic• When grown on 0.5% glycerin M tuberculosis growth improves• Sodium pyruvate improves the growth of both organism. Dr.T.V.Rao MD 31
  32. 32. On L J Medium• M.tuberculosis appear dry, rough raised irregular colonies• Appear wrinkled• They appear creamy white• Become yellowish• M.bovis appear as flat smooth, moist, white and break up easily Dr.T.V.Rao MD 32
  33. 33. Lowenstein Jensen Medium –Selective. Always in screw capped bottle. Bluish Green. Contains – Egg protein – Solidifying agent Mineral salts – Mg Sulphate, Mg citrate Asparagine Malachite Green – Selective agent Sterilized by - Inspissation Dr.T.V.Rao MD 33
  34. 34. On Liquid Medium•Appear as long serpentine cords in liquid medium•Virulent strains grow in a more dispersed manner. Dr.T.V.Rao MD 34
  35. 35. Resistance of Mycobacterium• Mycobacterium are killed at 600c in 15 – 20 mt• In sputum they survive for 10 – 30 mt• Relatively resistant to several chemicals including Phenol 5 %• Sensitive to Glutaraldehyde and Formaldehyde• Ethanol is suitable application to superficial surfaces and skin gloves Dr.T.V.Rao MD 35
  36. 36. Resistance to several agents• Bacilli survive in Droplets for 8 – 10 days• Survive in 5% phenol, 15% Sulphuric acid 3% Nitric acid,5% oxalic acid, 4% Sodium hydroxide Dr.T.V.Rao MD 36
  37. 37. Biochemical Tests on Mycobacterium spp• Niacin test – 10% cyanogens bromide and 4% Aniline in 96% ethanol are added to suspension of – C canary yellow color indicates positive test. Dr.T.V.Rao MD 37
  38. 38. Other Tests• Aryl sulphatase test – Positive in Atypical Mycobacterium• Bacilli grown in 0.001 tripotassium phenolpthalein disulphide / 2 N. Sodium hydroxide added drop by drop a pink color develops• Catalase peroxidase test – Differentiates Atypical from Typical Most Atypical are strongly Catalase positive Tubercle bacilli are weakly positive Tubercle bacilli are peroxidase positive – not atypical INH resistant strains are negative for test Dr.T.V.Rao MD 38
  39. 39. Catalase Test• 30 Vol of H2O2 and 0.2 % alcohol in distilled water is added to 5 ml of test culture• Effervescence indicates Catalase positive• Other test Amidase test Nitrate reduction test Dr.T.V.Rao MD 39
  40. 40. Antigenic Characters• Group specificity due to Polysaccharides• Type specificity to protein antigens• Delayed hypersensitivity to proteins• Related to each other species• Some relation between lepra and tubercle bacilli• Serology – Tests not useful Antigenic homogeneity between < bovis and M.microti Dr.T.V.Rao MD 40
  41. 41. Bacteriophages• There are 4 Bacteriophages A B C D• A worldwide• B. Europe and -American• C rare• I type nature between A and B and common in India• Phage 33 D M tuberculosis and not in BCG strains Dr.T.V.Rao MD 41
  42. 42. Molecular Typing• DNA finger printing differentiates different strains of Mycobacterium species• Treating the organism with Restriction endonuclease yields Nucleic acid fragments of varying length and strain specific• Use in epidemiological studies Dr.T.V.Rao MD 42
  43. 43. Finger printing Methods• Finger printing is done with Chromosomal insertion sequence IS 6110 present in most strains of Tubercle bacilli• Now entire genome of M tuberculosis is sequenced• Several Molecular methods are available for studies Dr.T.V.Rao MD 43
  44. 44. Genome of Mycobacterium tuberculosis Dr.T.V.Rao MD 44
  45. 45. How tuberculosis spreadsdisease. Like• Tuberculosis (TB) is a contagious the common cold, it spreads through the air. Only people who are sick with TB in their lungs are infectious. When infectious people cough, sneeze, talk or spit, they propel TB germs, known as bacilli, into the air. A person needs only to inhale a small number of these to be infected. Dr.T.V.Rao MD 45
  46. 46. Tuberculosis spread by Respiratory route Dr.T.V.Rao MD 46
  47. 47. Tuberculosis highly Communicable Disease.• Someone in the world is newly infected with TB bacilli every second.• Overall, one-third of the worlds population is currently infected with the TB bacillus.• 5-10% of people who are infected with TB bacilli (but who are not infected with HIV) become sick or infectious at some time during their life. People with HIV and TB infection are much more likely to develop TB. Dr.T.V.Rao MD 47
  48. 48. Pathology and Pathogenesis of Tuberculosis• Source of Infection – Open case of Pulmonary Tuberculosis.• Every open case has potential to infect 20 – 25 healthy persons before cured or dies• Coughing , Sneezing, or Talking.• Each act can spill 3000 infective nuclei in the air,• Infective particles are engulfed by Alveolar Macrophages. Dr.T.V.Rao MD 48
  49. 49. Spread of Tuberculosis Dr.T.V.Rao MD 49
  50. 50. Generation of Droplet Nuclei• One cough produces 500 droplets• The average TB patient generates 75,000 droplets per day before therapy• This falls to 25 infectious droplets per day within two weeks of effective therapy Dr.T.V.Rao MD 50
  51. 51. Dr.T.V.Rao MD 51
  52. 52. Predisposing Factors• Genetic basis,• Age• Stress,• Nutrition,• Co existing infections Eg HIV Dr.T.V.Rao MD 52
  53. 53. Mechanisms of Infection• Mycobacterium do not produce toxins.• Allergy and Immunity plays the major role.• Only 1/10 of the infected will get disease.• Cell Mediated Immunity plays a crucial role.• Humoral Immunity – not Important.• CD4 Cell plays role in Immune Mechanisms. Dr.T.V.Rao MD 53
  54. 54. Mechanisms of Infection• Within 10 days of entry of Bacilli clones of Antigen specific T Lymphocytes are produced• Can actively produce Cytokines, Interferon γ which activate Macrophages form cluster or Granuloma Dr.T.V.Rao MD 54
  55. 55. Dr.T.V.Rao MD 55
  56. 56. Tubercle with Caseous NecrosisTubercle bacilli Lymphocyte Giant cellsFully activated Partially activated macrophage macrophage Dr.T.V.Rao MD 56
  57. 57. Basis of Tubercle formation.• Tubercle is a Avascular granuloma Contain central zone of giant cells with or without caseation and peripheral zone of Lymphocytes and Fibroblasts.• Produce lesions may be Exudative or Productive Dr.T.V.Rao MD 57
  58. 58. Diagram of a Granuloma NOTE: ultimately a fibrin layer develops around granuloma (fibrosis), further “walling off” the lesion. Typical progression in pulmonary TB involves caseation, calcification and cavity formation.Dr.T.V.Rao MD 58
  59. 59. Tubercle dischargingBronchial tree TNF- a TNF- a Dr.T.V.Rao MD 59
  60. 60. Immunity in Tuberculosis.• CD4 T Lymphocytes with Th 1 or Th 2 secrete - 1 Cytokines,2 Interleukin 1,and 2 , 3 Interferons γ ,4.Tumor necrosis factor.• The mechanisms with Th 1 secrete Cytokines Activate Macrophages Results in protective Immunity, and contain Infection. Th 2 manifests with Delayed Hypersensitivity DTH causes Tissue destruction. and disease will progress. . Dr.T.V.Rao MD 60
  61. 61. Immunity in TuberculosisActivated Macrophages - Epitheliod cellsForms cluster a granulomaActivated macrophages turn into Giant cells.Granuloma contains necrotic tissue Dead macrophages cheese like caseation.Apoptosis of bacteria laden cellsContribute to protective immunity. Dr.T.V.Rao MD 61
  62. 62. Lesions in Tuberculosis • Exudative – and Productive• Exudative – Acute inflammatory reaction with edema fluid – contains Polymorphs- Lymphocytes – later Mononuclear cells.Bacilli are virulent - Host responds with DTH Injurious. Productive Type protective Immunity Dr.T.V.Rao MD 62
  63. 63. Primary Tuberculosis• Initial response• In Endemic countries Young children• Events of Primary complex 1 Bacilli are engulfed by Alveolar Macrophages 2 Multiply and give raise to Sub pleural focus of Tuberculosis,Pneumonia,involve lower lobes and lower part of upper lobes. Called as Ghon’s focus.The Hilar Lymph nodes are also involved Dr.T.V.Rao MD 63
  64. 64. Primary complex• This is known as the primary complex or primary infection. The patient will heal and a scar will appear in the infected loci. There will also be a few viable bacilli/spores may remain in these areas (particularly in the lung). The bacteria at this time goes into a dormant state, as long as the persons immune system remains active and functions normally this person isnt bothered by the dormant bacillus. Dr.T.V.Rao MD 64
  65. 65. Primary complex• Ghon’s focus with Enlarged lymph nodes appear after 3- 8 weeks after infection.• Heals in 2 – 6 months calcified,• Some bacteria remain alive and produce latent infections.• Infection activated in Immunosuppressed conditions Eg. HIV infections and AIDS• Can produce Meningitis, Miliary tuberculosis, other disseminated Tuberculosis. Dr.T.V.Rao MD 65
  66. 66. Reactivation of Tuberculosis• When a persons immune system is depressed., a secondary reactivation occurs. 85-90% of the cases seen which are of secondary reactivation type occurs in the lungs. Dr.T.V.Rao MD 66
  67. 67. Koch’s Phenomenon• Tuberculosis infected Guinea pig if injected with Living Tubercle bacilli• The site around the injection becomes necrotic.• Koch found the same reaction when injected with old Tuberculin ( heated and concentration of the tubercle bacilli )• It has produced the same reaction• This is called as Koch’s Phenomenon. Dr.T.V.Rao MD 67
  68. 68. Post Primary Tuberculosis• Mainly occurs due to Reactivation of Latent infection.• May also due to Exogenous reinfection• Differs from Primary Infection.• Leads to – Cavitations of Lungs, Enlargement of Lymph nodes,Expectoration of Bacteria laden sputumDissemination into Lungs and other extra pulmonary areas. Dr.T.V.Rao MD 68
  69. 69. Majority of the Tuberculosis are Pulmonary Dr.T.V.Rao MD 69
  70. 70. Multiorgan Involvement in Tuberculosis. Dr.T.V.Rao MD 70
  71. 71. Complication of Tuberculosis.1. Meningitis.2. Pleurisy,3. Involvement of Kidney,4. Spine ( Potts spine )5. Bone Joints,6. Miliary tuberculosis Dr.T.V.Rao MD 71
  72. 72. Symptoms and Sings of Tuberculosis Dr.T.V.Rao MD 72
  73. 73. Dr.T.V.Rao MD 73
  74. 74. Clinical Illness with Tuberculosis• Pulmonary Disease – Major manifestation with involvement of Lungs Hemoptysis, Chest pain Fever sweets Anorexia Cavity formation in Lungs Dr.T.V.Rao MD 74
  75. 75. Tuberculosis - Pneumothorax Dr.T.V.Rao MD 75
  76. 76. Extra pulmonary Tuberculosis• Bacteria on circulation leads to bacteremia leads to involvement of GUT, Genito urinary system, Meningitis Gastro Intestinal system, skin, Lymph nodes Bone marrow. Spinal infection Potts spine, Arthritis Dr.T.V.Rao MD 76
  77. 77. Tuberculosis - Lymphadenitis Dr.T.V.Rao MD 77
  78. 78. Epidemiology• An ancient disease, called as white plague• 1/3 of the world population is infected• 2 billion infected• Each year 9 lakhs to 1 million are infected• Poor nations phase the burnt of the disease.• In developing world > 4o% of the population is effected• 15 million suffer the disease• 3 million are highly infective. Dr.T.V.Rao MD 78
  79. 79. Diagnosis of Tuberculosis Dr.T.V.Rao MD 79
  80. 80. Types of specimens:-Sputum.- BAL.-Pleural effusions- Urine- Stool-CSF-Aspiration ( gastric – cold abscess)- Blood in case of haematogenous TB Dr.T.V.Rao MD 80
  81. 81. Laboratory Diagnosis1- Sputum smears stained by Z-N stainThree morning successive mucopurulent sputum samples are needed to diagnose pulmonary TB. Advantage: - cheap – rapid - Easy to perform - High predictive value > 90% - Specificity of 98%Disadvantages: - sputum ( need to contain 5000-10000 AFB/ ml.) - Young children, elderly & HIV infected persons may not produce cavities & sputum containing AFB. Dr.T.V.Rao MD 81
  82. 82. 2- Detecting AFB by fluorochrome stain using fluorescence microscopy:The smear may be stained by aura mine-O dye. In this method the TB bacilli are stained yellow against dark background & easily visualized using florescent microscope. Advantages: - More sensitive - RapidDisadvantages: - Hazards of dye toxicity - more expensive - must be confirmed by Z-N stain Dr.T.V.Rao MD 82
  83. 83. 3- Cultures on L J media Lowenstein –Jensen medium is an egg based mediawith addition of salts, 5 % glycerol, Malachite green & penicillin.Advantages: - Specificity about 99 % - More sensitive (need lower no. of bacilli 10-100 / ml) - Can differentiate between TB complex & NTM using biochemical reactions - Sensitivity tests for antituberculous drugs ( St, INH, Rif., E)Disadvantages: Slowly growing ( up to 8 weeks ) Dr.T.V.Rao MD 83
  84. 84. Tuberculin TestInterpretation:*A positive test indicates previous exposure and carriage of T.B.* A negative tuberculin test excludes infection in suspected persons* Tuberculin positive persons may develop reactivation type of T.B.* Tuberculin negative persons are at risk of gaining new infection* False positive reactions are mainly due to: - Infection with nontuberculous mycobacteria* False negative reactions may be due to: - Sever tuberculosis infection (Miliary T.B.) - Hodgkin’s disease - Corticosteroid therapy - Malnutrition - AIDS* Children below 5 years of age with no exposure history: - Positive test must be regarded suspicious Dr.T.V.Rao MD 84
  85. 85. Tuberculin Testing - Limitations• False positive reactions are mainly due to:• - Infection with nontuberculous mycobacteria• * False negative reactions may be due to:• - Sever tuberculosis infection (Miliary T.B.) - Hodgkin’s disease• - Corticosteroid therapy - Malnutrition - AIDS• * Children below 5 years of age with no exposure history:• - Positive test must be regarded suspicious Dr.T.V.Rao MD 85
  86. 86. Recent Methods for DiagnosisI – BACTEC 460 ( rapid radiometric culture system ) specimens are cultured in a liquid medium (Middle brook7H9 broth base )containing C14 – labeled palmitic acid & PANTA antibiotic mixture. Growing mycobacteria utilize the acid, releasing radioactive CO2 which is measured as growth index (GI) in the BACTEC instrument. The daily increase in GI output is directly proportional to the rate & amount of growth in the medium. Dr.T.V.Rao MD 86
  87. 87. III Polymerase Chain Reaction (PCR) & Gene probe Nucleic acid probes & nucleic acid amplification tests in which polymerase enzymes are used to amplify ( make many copies of specific DNA or RNA sequences extracted from mycobacterial cells.Advantages: - Rapid procedure - High sensitivity (1-10 ( 3 – 4 hours) bacilli / ml sputum) Dr.T.V.Rao MD 87
  88. 88. Tuberculosis and HIV infection• HIV association has become a threat to the developed countries too• HIV association will lead to rapid spread of tuberculosis Dr.T.V.Rao MD 88
  89. 89. HIV Considerations• HIV is the strongest risk factor for progression to active disease• HIV kills CD4+ T Helper cells which normally inhibit M. tuberculosis• HIV interferes with PPD skin test• Protease inhibitors interfere with rifampin Dr.T.V.Rao MD 89
  90. 90. MDR tuberculosis• Multidrug resistant tuberculosis has become a global threat.• In 1993 WHO declared Tuberculosis a Global emergency• Animals shed the bacilli in Milk, human’s get infected after drinking the unsterilized Milk• Pasteurization has reduced the incidence of Bovine tuberculosis. Dr.T.V.Rao MD 90
  91. 91. Why Tuberculosis continues to be Important• Someone in the world is newly infected with TB bacilli every second.• Overall, one-third of the worlds population is currently infected with the TB bacillus.• 5-10% of people who are infected with TB bacilli (but who are not infected with HIV) become sick or infectious at some time during their life. People with HIV and TB infection are much more likely to develop TB. Dr.T.V.Rao MD 91
  92. 92. TreatmentDrugs used :1- First line drugs : - Isoniazid - Rifampicin - Pyrazinamide - Ethambutol - Streptomycin2- Second line drugs (more toxic and less effective): - Kanamycin - capreomycin - Cycloserin - ethionamide - ciprofloxacin - Ofloxacin* Noncompliance (failure to complete the course): Directly observed therapy (DOT) Health care workers observe the medication Dr.T.V.Rao MD 92
  93. 93. Immuno-prophylaxis• Intradermal injection of live attenuated vaccine Bacille Calmette-Guerin (BCG).• The strain causes self limited lesion and induces hypersensitivity & immunity.• Coverts tuberculin negative person to positive reactor.• Immunity lasts for 10-15 years. Immunity 60- 80%• Some studies proved BCG is doubtful value in Dr.T.V.Rao MD 93 prevention of Tuberculosis
  94. 94. BCG• Given at birth without tuberculin testing• Protects against TB, the disease runs milder course in protected, prevents skeletal, meningeal & miliary forms.• Also found useful in leprosy, leukaemias and other malignancies by non-specific stimulation of RE system. Dr.T.V.Rao MD 94
  95. 95. • Programme created by Dr.T.V.Rao MD for Medical and Paramedical students in the Developing World • Email • Dr.T.V.Rao MD 95
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