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Pulmonary Tuberculosis


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Pulmonary Tuberculosis

  1. 1. Tuberculosis Robert L. Copeland, Jr., Ph.D. Brian Tracy . Hong Fan Department of Respiratory Diseases, West China Hospital, Sichuan University
  2. 2. Introduction: Infects 1/3 to ½ of world population..! 3 million deaths due to TB every year Under privileged population - Crowding, Poverty, malnutrition, single male..! Since 1985 incidence is increasing in west AIDS, Diabetes, Immunosuppressed patients, Diabetes, Drug resistance. Fan H.
  3. 3. Tuberculosis (TB) remains the leading cause of death worldwide from a single infectious disease agent. Indeed up to 1/2 of the world's population is infected with TB. The registered number of new cases of TB worldwide roughly correlates with economic conditions: the highest incidences are seen in those countries of Africa, Asia, and Latin America with the lowest gross national products. WHO estimates that eight million people get TB every year, of whom 95% live in developing countries. An estimated 2 million people die from TB every year. Fan H.
  4. 4. It is estimated that between 2000 and 2020, nearly one billion people will be newly infected, 200 million people will get sick, and 35 million will die from TB - if control is not further strengthened. The mechanisms, pathogenesis, and prophylaxis knowledge is minimal. After a century of decline TB is increasing and there are strains emerging which are resistant to antibiotics. This excess of cases is attributable to the changes in the social structure in cities, the human immunodeficiency virus epidemic, and failure of most cities to improve public health programs, and the economic cost of treating. Fan H.
  5. 5. With the increased incidence of AIDS, TB has become more a problem in the U.S., and the world. It is currently estimated that 1/2 of the world's population (3.1 billion) is infected with Mycobacterium tuberculosis. Mycobacterium avium complex is associated with AIDS related TB. Fan H.
  6. 6. TB is an ancient infectious disease caused by Mycobacterium tuberculosis. It has been known since 1000 B.C., so it not a new disease. Since TB is a disease of respiratory transmission, optimal conditions for transmission include: overcrowding poor personal hygiene poor public hygiene Fan H.
  7. 7. Transmission Pulmonary tuberculosis is a disease of respiratory transmission, Patients with the active disease (bacilli) expel them into the air by: coughing, sneezing, shouting, or any other way that will expel bacilli into the air Fan H.
  8. 8. Once inhaled by a tuberculin free person, the bacilli multiply 4 -6 weeks and spreads throughout the body. The bacilli implant in areas of high partial pressure of oxygen: lung renal cortex reticuloendothelial system Fan H.
  9. 9. This is known as the 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 person's immune system remains active and functions normally this person isn't bothered by the dormant bacillus. When a person's immune system is depressed., a secondary reactivation occurs. 85-90% of the cases seen which are of secondary reactivation type occurs in the lungs. Fan H.
  10. 10. Fan H.
  11. 11. Pathogenesis of TB: Type IV hypersensitivity – T cells – Macrophages Granuloma Activated macrophages – epithelioid cells. Remain viable inside macrophages (Mycolic acid wax coat) Cord Factor - surface glycolipid Antigenic. Self destruction by lysosomal enzymes. Fan H.
  12. 12. Fan H.
  13. 13. Hypersensitity – Immunity Fan H.
  14. 14. Microbiology of TB: Mycobacteria – ‘fungus like.. Bacilli, Aerobic, non motile, no toxins, no spore. Mycolic acid wax in cell wall Carbol dye - Acid & alcohol fast (AFB) M. tuberculosis & M. bovis M. avium, M.intracellulare in AIDS - Atypical TB Fan H.
  15. 15. AFB - Ziehl-Nielson stain
  16. 16. Colony Morphology – LJ Slant
  17. 17. Classification of TB 1. Primary Pulmonary TB 2. Miliary TB (acute, subacute, chronic) 3. Secondary TB (invasive, carvitary, caseation , Tuberculous Granulomas …) 4. Tuberculous Pleuritis 5. Extra-pulmonary TB (bone, joints, renal, adrenal,skin… ) Fan H.
  18. 18. Primary tuberculosis In a non immunized individual – children* adult* Deep inhalation of airborne droplet ~ 3 microns. Bacilli locate in the subpleural mid zone of lung Localized "atypical" pneumonia Brief acute inflammation – neutrophils. 5-6 days invoke granuloma formation. 2 to 8 weeks – healing – single round -Ghon focus. If lymph node is also involved Ghon complex. Fan H.
  19. 19. Primary or Ghon’s Complex Primary tuberculosis is the pattern seen with initial infection with tuberculosis in children. Reactivation, or secondary tuberculosis, is more typically seen in adults. Fan H.
  20. 20. Primary Tuberculosis In Non Immunized individuals (Children) Primary Tuberculosis: Self Limited disease Ghons focus, complex or Primary complex. Primary Progressive TB ( in US. ) Miliary TB and TB Meningitis. Common in malnourished children 10% of adults, Immuno-suppressed individuals Fan H.
  21. 21. Secondary Tuberculosis: Post Primary in immunized individuals. Cavitary Granulomatous response. Reactivation or Reinfection Apical lobes or upper part of lower lobes – O2 Caseation, cavity - soft granuloma Pulmonary or extra-pulmonary Local or systemic spread / Miliary Vein – via left ventricle to whole body Artery – miliary spread within the lung Fan H.
  22. 22. Secondary Tuberculosis: Reactivation occurs in 10-15% of patients. Most commonly males 30-50 y Slowly Progressive (several months) Cough, sputum, Low grade fever, night sweats, fatigue and weight loss. Hemoptysis or pleuritic pain = severe disease Fan H.
  23. 23. Ghon Complex Fan H.
  24. 24. Miliary TB
  25. 25. Miliary TB Millet like – grain. Extensive micro spread. Through blood or bronchial spread Low immunity Pulmonary or Systemic types.
  26. 26. Miliary TB Lung
  27. 27. Cavitary Tuberculosis When necrotic tissue is coughed up cavity. Cavitation is typical for large granulomas. Cavitation is more common in the secondary reactivation tuberculosis - upper lobes. Fan H.
  28. 28. Fan H.
  29. 29. Fan H.
  30. 30. Fan H.
  31. 31. Tuberculous Granulomas
  32. 32. Caseation Necrosis
  33. 33. Epitheloid cells in Granuloma
  34. 34. Cells in Granuloma
  35. 35. Morphology of Granuloma 1. Rounded tight collection of chronic inflammatory cells. 2. Central Caseous necrosis. 3. Active macrophages - epithelioid cells. 4. Outer layer of lymphocytes, plasma cells & fibroblasts. 5. Langhans giant cells – joined epithelioid cells. Fan H.
  36. 36. Tuberculous Granuloma
  37. 37. Cavitary Secondary TB
  38. 38. Systemic Miliary TB
  39. 39. Adrenal TB - Addison Disease
  40. 40. Spinal TB - Potts Disease
  41. 41. Diagnosis of TB Clinical features are not confirmatory. Zeil Nielson Stain - 1x104/ml, 60% sensitivity Release of acid-fast bacilli from cavities intermittent. 3 negative smears to assure low infectivity* Culture most sensitive and specific test. Conventional Lowenstein Jensen media 3-6 wks. Automated techniques within 9-16 days PCR is available, but should only be performed by experienced laboratories PPD for clinical activity / exposure sometime in life. Fan H.
  42. 42. PPD Tuberculin Testing Sub cutaneous Weal formation Itching – no scratch. Read after 72 hours. Induration size. 5-10-15mm (non-ende) < 72 hour is not diag* +ve after 2-4 weeks. BCG gives + result.
  43. 43. PPD Testing
  44. 44. Granuloma or LH giant cell is not pathagnomonic of TB…! Foreign body granuloma. Fat necrosis. Fungal infections. Sarcoidosis. Crohns disease.
  45. 45. "Troubles are often the tools by which God fashions us for better things." - Henry Ward Beecher
  46. 46. Classification of Drugs 3 Groups depending upon the degree of effectiveness and potential side effects First Line: (Primary agents) are the most effective and have lowest toxicity. Isoniazid (H), Rifampin(R) Second Line: Less effective and more toxic effects include (in no particular order): p-amino salicylic acid, Streptomycin(S), pyrazinamide(Z), Ethambutol(E), Third Line are least effective and most toxic. Amikacin, Kanamycin, Capreomycin, Viomycin, Kanamycin, Cycloserine Fan H.
  47. 47. Isoniazid Considered the drug of choice for the chemotherapy of TB. discovered in 1945 a hydrazide of isonicotonic acid is bacteriostatic for resting bacilli, bactericidal for growing bacilli. Fan H.
  48. 48. Treatment 2HRZE/4HRE, 2HRSE/4HRE ( 6---18months ) in China (in the U.S. ,Isoniazid, Ethambutol, & Rifampin are given for 2 months. Isoniazid & Rifampin are given for 4 months. If you suspect resistance to isoniazid use (HRZE)Isoniazid, Ethambutol, Rifampin & Parazinamide. Incidence of drug resistance is 2-5% in the U.S. ) Prolonged bed rest is not necessary or helpful in obtaining a speedy recovery. The patient must be seen at regular and frequent intervals to follow the course of the disease and treatment. Look for toxic effects Fan H.
  49. 49. Chemoprophylaxis of TB Used only in high risk groups Household members and other close contacts of a patient with active TB. A positive skin test in persons less than 35 years. A positive skin test reactive in the immunosuppressed, persons with leukemia, and Hodgkin's Disease, HIV + patients with a positive TB test, ( INH 300mg/d, 6—8m. ) Fan H.
  50. 50. The drug of choice for chemoprophylaxis is isoniazid. Prophylaxis uses only one drug. In patients who are HIV+ and TB+ and have the disease; they are treated for a minimum of 9 months, 2HR/7HR?? ? (The first 2 months using HR(isoniazid and rifampin) and for the next 7 months or longer, use only 2 or 3 of the 2nd/3rd line drugs and Isoniazid/Rifampin. ) Fan H.
  51. 51. Conclusions: A chronic, common, infectious disease - Weight loss, fever, night sweats, lung damage. Commonest fatal infectious disease in the world. CXR – apical of upper lob, basal of lower lob lesions (CXR atypical AIDS) AIDS, Diabetes, malnutrition (poverty), crowding. Five / (Two forms Primary, Secondary in US.) Pulmonary,miliary,invasive,pleuritis,extrapulmonary,. AFB(sputum stain +) - infectiousness - isolation to prevent selection of resistance Prevention depends on PPD & INH prophylaxis Fan H.
  52. 52. WARNING! Rifampin and Isoniazid are the most effective drugs for the treatment of TB, The drug enjoys high patient compliance and acceptability. But these 2 drugs should never be given alone! They are always used in combination because resistance occurs to one drug alone very rapidly. They are used in combination with each other initially as well as other drugs. Bacilli must become resistant to two drugs in order to remain viable. Statistically, the chances are verv small of the bacilli becoming resistant to both. . Prophylaxis is with one drug usually isoniazid. Fan H.
  53. 53. What is New…? 14-30% of TB patients also HIV infected. New drugs - Rifapentine, Interferons, Thalidomide. Immune therapy : Killed M. vaccine stimulates CD8 cells (increased INF and IL-12). The genome of TB has been identified (~4000 genes) potential to develop new vaccines and tests. Fan H.
  54. 54. "When you are faced by the consequences of past choices, You see the gift of a lesson rather than a curse of a fall. Brian Tracy