12 Tuberculosis Tanweiping


Published on

Published in: Health & Medicine, Technology
1 Like
  • Be the first to comment

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

12 Tuberculosis Tanweiping

  1. 1. Childhood Tuberculosis Mbbs.weebly.com
  2. 2. Definition <ul><li>Tuberculosis is caused by Mycobacterium tuberculosis , isolated by Robert Koch in 1882 , M.bovis(seldom) </li></ul><ul><li>mainly involves the lungs, but may spread to other organs </li></ul><ul><li>consumption </li></ul>
  3. 3. Epidemiology <ul><li>19th century, 25% deaths by TB </li></ul><ul><li>1940s, effective medicines </li></ul><ul><li>2 billion people—one third of the world's population—been exposed TB </li></ul><ul><li>Annually, 8 million become ill with tuberculosis, 2 million people die </li></ul><ul><li>The morbidity / mortality are high in developing countries </li></ul><ul><li>incidences rates 113 per 100,000 in China </li></ul>
  4. 4. Epidemiology <ul><li>Age:60% Infant - <5yr </li></ul><ul><li>Male:female-1:1 (adults male predominate) </li></ul><ul><li>TB adults exposure </li></ul><ul><li><2yr,HIV coinfection, immunocompromise, malnutrition </li></ul><ul><li>HIV/AIDS, </li></ul><ul><li>drug-resistant </li></ul>
  5. 5. Etiology <ul><li>Tubercle bacillus: </li></ul><ul><li>aerobic,non-Motile,non-spore-forming, high </li></ul><ul><li>lipid content </li></ul><ul><li>acid-fast, weak Gram(+) </li></ul><ul><li>grows slowly </li></ul><ul><li>Sensitive to heat/sunlight tolerate in humid or dry or cold. withstand weak disinfectants and survive in a dry state for weeks . </li></ul>
  6. 6. Dr. Robert Koch discovered the tuberculosis bacilli in 1882 He received the Nobel Prize in physiology or medicine in 1905 for this discovery
  7. 7. <ul><li>Tuberculosis is transmitted by airborne droplet nuclei(containing tubercle bacilli ) </li></ul><ul><li>prolonged, frequent, or intense contact </li></ul>
  8. 8. <ul><li>Many droplet nuclei are capable of floating in environment for several hours </li></ul><ul><li>Large particles may be inhaled by person </li></ul><ul><li>breathing the same air and impact on the </li></ul><ul><li>trachea or wall of the upper airway </li></ul>
  9. 9. The transmission is determined <ul><li>The probability of contact with active — not latent — TB </li></ul><ul><li>intimacy and duration of contact </li></ul><ul><li>effectiveness of ventilation </li></ul><ul><li>number s and virulence of the M. tuberculosis strain in infectious droplets </li></ul>
  10. 10. Pathogenesis <ul><li>tubercle bacillus </li></ul>Human immunity
  11. 11. Pathogenesis <ul><li>90% infected with Mycobacterium tuberculosis asymptomatic, latent TB infection 10% progress to TB disease </li></ul><ul><li>if untreated, the death rate for these active TB cases is more than 50% </li></ul>
  12. 12. Pathogenesis <ul><li>mycobacteria -> pulmonary alveoli -> replicate within macrophages -> picked up by dendritic cells -> transport to local LN -> spread through bloodstream to other tissues/organs -> secondary TB lesions </li></ul><ul><li>primary site of infection : upper part of the lower lobe, or lower part of the upper lobe of lung </li></ul><ul><li>secondary TB lesions: apex of the upper lobes , peripheral lymph nodes, kidneys, brain, and bone </li></ul>
  13. 13. Human Immunity /hypersensitivity after TB infection <ul><li>Specific immunity after infected or given BCG vaccine </li></ul><ul><li>Cell-mediate immunity develops within 4-8 weeks after infected with bacillus </li></ul><ul><li>Many immunologic cells: Macrophages, T/B lymphocytes, fibroblasts involved </li></ul>
  14. 14. Two types of cells are essential in the formation of TB <ul><li>Macrophages: directly phagocytize TB and processing and presenting antigens to T lymphocyte </li></ul><ul><li>T lymphocytes(CD4+): induce protection through the production of lymphokines </li></ul>
  15. 15. T lymphocytes(CD4+) <ul><li>Many lymphokines are involved in tuberculosis, the interplay of these cytokines determine the hosts response for example </li></ul><ul><li>IL-1 is related to fever </li></ul><ul><li>IL-6 is related to hyperglobulinemia </li></ul><ul><li>TNF is related to the killing of mycobacteria formation of granulomas </li></ul><ul><li>other cytokines including IL-4,IL-5,IL-10 can promote humoral immunity </li></ul>
  16. 16. <ul><li>Genetic factors ( HLA-BW35) play a key role in innate non-immune resistance to infection with M. Tuberculosis </li></ul><ul><li>These genes may have a role in determining susceptibility to tuberculosis </li></ul>
  17. 17. Basic pathologic changes <ul><li>infiltration -> hyperplasia( granuloma) , ulceration or calcification in different stage </li></ul><ul><li>host defense < bacterias, caseating ulceration(caseous necrosis ) -> fibrosis </li></ul><ul><li>host defense > bacteria, granuloma calcification </li></ul>
  18. 18. A characteristic tubercle at low magnification ( A ) and in detail ( B ) central caseation surrounded by epithelioid and multinucleated giant cells(C) mycobacteria with acid-fast stains ( D ).
  19. 19. Progression of tuberculosis <ul><li>Absorption </li></ul><ul><li>Fibrosis </li></ul><ul><li>Calcification </li></ul><ul><li>Deterioration: enlargement of infected aeras and appear newer infiltrated regions or spreading. </li></ul>
  20. 20. Five common clinical patterns <ul><li>1. Primary pulmonary tuberculosis (Primary Complex and </li></ul><ul><li>Bronchial Lymphnode-Tuberculosis) </li></ul><ul><li>2. Milliary Tuberculosis (acute, subacute and chronic hematogenous pulmonary tuberculosis) </li></ul><ul><li>3. secondary pulmonary tuberculosis </li></ul><ul><li>Infiltrative pulmonary tuberculosis </li></ul><ul><li>Chronic fibrocavenous pulmonary tuberculosis </li></ul><ul><li>4.Tuberculous pleuritis </li></ul><ul><li>5.Extrapulmonary tuberculosis </li></ul>
  21. 21. Diagnosis <ul><li>History and Clinical Manifestations </li></ul><ul><li>Tuberculin testing </li></ul><ul><li>Lab examination </li></ul><ul><li>X-r ay </li></ul><ul><li>bronchoscopy </li></ul><ul><li>Puncture of adenopathy </li></ul>
  22. 22. History /Clinical Manifestations <ul><li>systemic signs : fever, weight loss, fatigue, night sweats, wasting </li></ul><ul><li>TB Contaction : adults in family </li></ul><ul><li>History of BCG Vaccination </li></ul><ul><li>Acute infectious disease recently : measles,whooping cough </li></ul><ul><li>Allergy to TB : erythema nodosum 、 herpetic conjunctivitis </li></ul>
  23. 23. Tuberculin skin test <ul><li>a skin test to determine past or present infection with the tuberculosis bacterium; based on hypersensitivity of the skin to tuberculin </li></ul><ul><li>Method of test protein purified derivative PPD 0.1ml intradermal injection </li></ul><ul><li>Site : internal side of medium-distal 1/3 left forearm </li></ul><ul><li>6 - 10mm </li></ul><ul><li>Result : 48-72hrs, transverse </li></ul><ul><li>diameter </li></ul>
  24. 24. Result is read by measuring the diameter of induration 48-72hrs <ul><li>Induration <5mm negative </li></ul><ul><li>Induration 5-9mm(+) </li></ul><ul><li>Induration 10-19mm(++) </li></ul><ul><li>Induration 》 20mm (+++) </li></ul><ul><li>A positive tuberculin skin test indicates </li></ul><ul><li>tuberculous infection, with or without disease </li></ul>
  25. 25. <ul><li>Tuberculin testing </li></ul><ul><li>A positive tuberculin test is of great use in children, with limited diagnostic significance in adults </li></ul>
  26. 26. Clinical Significance <ul><li>Positive </li></ul><ul><li>Negative </li></ul>
  27. 27. Positive Reaction : indicates TB exposure <ul><li>BCG Vaccination </li></ul><ul><li>Children and adolescents(++) exposed to TB </li></ul><ul><li>Infant﹤3yrs (++) recent infection </li></ul><ul><li>(+++) Active TB infectin </li></ul><ul><li>(-) -> (+) , or Induration<10mm ->>10mm, ↑>6mm recent infection </li></ul>
  28. 28. Negative Reaction <ul><li>Never exposed to TB </li></ul><ul><li>Within 4-8wks of primary infectin </li></ul><ul><li>False negative:compromised immunity </li></ul><ul><li>Technique failure or PPD invalidated </li></ul>
  29. 29. PPD reaction of natural TB infection and BCG vaccination <ul><li>Natural infection </li></ul><ul><li>stronge </li></ul><ul><li>Induration >10-15mm </li></ul><ul><li>deep red 、 regular margin 、 hard </li></ul><ul><li>pigmentation </li></ul><ul><li>Long duration > 7-10d </li></ul><ul><li>Less change </li></ul><ul><li>BCG vaccination </li></ul><ul><li>weak </li></ul><ul><li>Induration 5-9mm </li></ul><ul><li>light red 、 unregular margin 、 soft </li></ul><ul><li>Short duration:2-3d </li></ul><ul><li>Become weak gradually,disappear3-5y </li></ul>
  30. 30. Laboratory examinations <ul><li>Sputum examination acid-fast staining </li></ul><ul><li>PCR test to detect TB DNA </li></ul><ul><li>TB antibody testing </li></ul><ul><li>ESR </li></ul><ul><li>Blood Routine </li></ul>
  31. 31. Chest radiography <ul><li>Chest X-ray: most important method to detect TB </li></ul><ul><li>Characteristics ,area, degree of activity or progress </li></ul><ul><li>Differentiation with other disease </li></ul><ul><li>Follow the effectivity of therapy </li></ul>
  32. 32. bronchoscopy <ul><li>Endobrochial tuberculosis </li></ul><ul><li>tuberculous tracheobronchial lymphadenitis </li></ul>
  33. 33. Puncture of peripherial LN <ul><li>Tubercle </li></ul><ul><li>caseous necrosis </li></ul>
  34. 34. Treatment <ul><li>Common therapy : </li></ul><ul><li>Nutrition 、 Rest </li></ul><ul><li>Ventilation </li></ul><ul><li>Isolation </li></ul>
  35. 35. Chemotherapy <ul><li>goal : Kill TB </li></ul><ul><li>Limit TB from spreading </li></ul><ul><li>principles : </li></ul><ul><li>earlier, appropriate </li></ul><ul><li>Combination, Full course </li></ul><ul><li>regularly and Staged . </li></ul>
  36. 36. Classification of antitubercular drug <ul><li>bactericidal </li></ul><ul><li>( 1 ) complete bactericidal : </li></ul><ul><li>INH 、 RFP </li></ul><ul><li>( 2 ) semi- bactericidal : </li></ul><ul><li>SM : alkaline, fast propagation, </li></ul><ul><li>intracellular TB </li></ul><ul><li>PZA : Acidic 、 slow growth </li></ul><ul><li>intracellular TB </li></ul>
  37. 37. <ul><li>medicines are classified as first-line and second-line agents </li></ul><ul><li>First-line essential antituberculous agents are the most effective and are necessary components of </li></ul><ul><li>any short-course therapeutic regimen </li></ul>
  38. 38. <ul><li>First-line medicines include </li></ul><ul><li>Isoniazid, rifampin, </li></ul><ul><li>pyraziniamide,streptomycine </li></ul><ul><li>Second-line medicines include </li></ul><ul><li>ethambutal, para-amino-salicylic acid, </li></ul><ul><li>kanamycin, amikacin and ects. </li></ul><ul><li>Newer antituberculous drugs </li></ul><ul><li>rifapentine, rifabutin quinolones </li></ul>
  39. 39. Isoniazid (INH) first-line drug <ul><li>Isoniazid is a principal agent used to treat TB </li></ul><ul><li>It is universally accepted for initial treatment </li></ul><ul><li>Now considered the best anti-TB drug </li></ul><ul><li>It should be included in all TB treatment regmens unless the organism is resistant </li></ul>
  40. 40. Advantages <ul><li>Inexpensive </li></ul><ul><li>Readily synthesized </li></ul><ul><li>Availabe worldwide </li></ul><ul><li>Highly selective for mycobacteria </li></ul><ul><li>Well tolerated(about only 5% of patients exhibiting adverse effects ) </li></ul>
  41. 41. Dosage <ul><li>Tuberculosis organization have recommended </li></ul><ul><li>5 mg/kg daily for both groups </li></ul><ul><li>Generally, 300mg daily oral dose is adopted </li></ul>
  42. 42. Adverse effects <ul><li>The two most important adverse effects of isoniazid therapy are hepatotoxicity </li></ul><ul><li>periphral neuropathy </li></ul><ul><li>We must measure liver enzymes before </li></ul><ul><li>administrating and during treatment </li></ul><ul><li>periods(usually monthly measure) </li></ul><ul><li>If the liver enzymes level is higher than </li></ul><ul><li>normal,the drug must be discontinued </li></ul>
  43. 43. Rifampin (RFP) first-line drug <ul><li>It is also considered the most important and potent antituberculous agent </li></ul><ul><li>Like isoniazid it is bactericidal and highly effective </li></ul><ul><li>Unlike isoniazid, it is also effective against most other mycobacteria as well as other organisms </li></ul>
  44. 44. Chemotherapy Regimens <ul><li>Standard regimen : </li></ul><ul><li>asymptomatic primary infection </li></ul><ul><li>INH 、 RFP and/ ( or ) EMB </li></ul><ul><li>9-12 months </li></ul>
  45. 45. Two Stage Therapy <ul><li>Active primary TB 、 Disseminated TB 、 TB meningitis </li></ul><ul><li>Enforcement stage : 3-4 bactericidal , 3-4m </li></ul><ul><li>Consolidation stage : 2 drug , 12-18m </li></ul>
  46. 46. Short-term Therapy <ul><li>2 or 3 drugs killing of organisms + 1 </li></ul><ul><li>drug restraint of organisms </li></ul><ul><li>Mild/moderate with small infiltrates and thin wall cavities : </li></ul><ul><li>INH+RFP+SM(EMB) (PZA) 2 M or </li></ul><ul><li>INH+RFP 4 -7 M </li></ul><ul><li>extensive /severe, large areas of caseation or thick-walled cavities are identified: </li></ul><ul><li>INH+RFP+SM+EMB(PZA) 2 M or </li></ul><ul><li>INH+RFP 4 -7 M </li></ul>
  47. 47. Prevention <ul><li>Prevention of Tuberculosis : Vaccination </li></ul><ul><li>BCG Vaccination can obtain immunity acquired for tubercle bacillus. one of the most important tuberculosis prevention </li></ul><ul><li>Vaccination target: infants children and youngster of tuberculin negative (vaccination is of course of no use in tuberculin-positive persons) </li></ul>
  48. 48. Prevention <ul><li>Finding patients earlier </li></ul><ul><li>Treatment and management of patients </li></ul><ul><li>Prevention with medicines </li></ul><ul><li>The systemic organization of prevention </li></ul>
  49. 49. Prophylatic chemotherapy <ul><li>Intimate contact with family members suffering active TB </li></ul><ul><li><3y infant PPD test(++) without BCG viccination </li></ul><ul><li>PPD test (-) -> (+) recently </li></ul><ul><li>PPD test(++) accompanied by Tb toxic symptoms </li></ul><ul><li>PPD test(++) , suffered measles,whooping cough </li></ul><ul><li>PPD test(++) and need long term steroid therapy </li></ul>
  50. 50. <ul><li>Regimen: </li></ul><ul><li>INH : 10mg/kg.d , 6-9m </li></ul>
  51. 51. Tuberculous meningitis
  52. 52. Pathogenesis <ul><li>Spreading through bloodstream </li></ul><ul><li>Rupture of TB lesion->bacteria enter choroids plexuses -> CSF </li></ul><ul><li>Extension from nearby organ infected with TB </li></ul>
  53. 53. Clinical Manifestation <ul><li>The 1st Stage: 1-2wks </li></ul><ul><li>change of character:irritability, </li></ul><ul><li>Tb toxic symptom </li></ul><ul><li>Headaches ( vomiting 、 </li></ul><ul><li>drowsiness ) </li></ul>
  54. 54. The 2nd Stage 1-2wks <ul><li>Meningeal irritation stage </li></ul><ul><li>Increased ICP: Headaches,vomiting, drowsiness, seizure, nuchal rigidity, back pain, Kerning sign, Brudzinski sign. </li></ul><ul><li>Cranial Nerve palsy </li></ul><ul><li>Encephalitis:disorentation,movement disorders, speech impaiment, papilledema </li></ul>
  55. 55. The 3rd Stage <ul><li>Coma stage 1-3wks </li></ul><ul><li>coma, hemiplegia, paraplegia, convulsion consumption, abnormal metabolise of electrolyte </li></ul><ul><li>hypertenion, decerebrate posture </li></ul><ul><li>brain hernia->death </li></ul>
  56. 56. Diagnosis <ul><li>Medical history </li></ul><ul><li>Clinical manifestation </li></ul><ul><li>CSF examination </li></ul><ul><li>X -ray check </li></ul><ul><li>CT or MRI scanning </li></ul><ul><li>Tuberculin test </li></ul>
  57. 57. Differentiation diagnosis <ul><li>Meningococcal Meningitis </li></ul><ul><li>Viral Meningitis </li></ul><ul><li>cryptococcal meningitis </li></ul><ul><li>Cerebral tumor </li></ul>
  58. 58. Treatment <ul><li>General therapy </li></ul><ul><li>Anti-tuberculous therapy </li></ul><ul><li>Decreasing intracranial pressure </li></ul><ul><li>corticosteroids </li></ul><ul><li>Anti-symptomatic therapy </li></ul><ul><li>Follow -up </li></ul>
  59. 59. Anti-tuberculous therapy <ul><li>1、 The initial stage : </li></ul><ul><li>  3-4 m </li></ul><ul><li>  INH、RFP、PZA、SM </li></ul><ul><li>2、 The 2nd stage </li></ul><ul><li>  INH、RFP </li></ul><ul><li>  12 m </li></ul>
  60. 60. Latent infection of tuberculosis <ul><li>A patient is infected with Mycobacterium tuberculosis , but does not have active disease </li></ul><ul><li>Patients with latent tuberculosis are not infectious </li></ul><ul><li>The main risk is that approximately 10% of these patients will go on to develop active tuberculosis at a later stage of their life </li></ul><ul><li>The identification and treatment of people with latent TB is an important part of controlling this disease. </li></ul>
  61. 61. Miliary tuberculosis in an infant whose uncle also had tuberculosis. There is adenopathy in addition to the millet seed–like lesions
  62. 63. A posteroanterior (A) and lateral (B) chest radiograph of a child with hilar adenopathy caused by Mycobacterium tuberculosis.
  63. 64. Hilar and mediastinal adenopathy and a partial segmental lesion in a child with tuberculosis
  64. 65. Lobar pneumonia with bowing of the horizontal fissure in a child with tuberculosis. a secondary bacterial pneumonia may have been present
  65. 66. Tuberculous pleural effusion in a teenage girl. The pleural biopsy had caseating granulomas
  66. 67. A magnetic resonance image of tuberculoma in a child with culture-positive tuberculous meningitis. The child's presenting signs and symptoms included fever, altered mental status, and hemiparesis
  67. 68. Thank you