Φυματίωση - Παθογένεια, Κλινική εικόνα, Διάγνωση

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  1. 1.
  2. 2. WHO estimates: - 1997: 8x106 1999: 8.4x106 2011: 8.7x106 - : 1.7x109 (1/3 ) - LTBI: 95% MDR-MTB: R XDR-MTB: (kanamycin, amikacin, kapreomycin) N Engl J Med 2013;36
  3. 3. N Engl J Med 2013;36
  4. 4. N Engl J Med 2013;36
  5. 5. HIV/TB: - HIV - IV- 26-31 HIV- - LTBI HIV- (- ) 10% - 2013: 9x106 1.1x106 (13%) HIV- - HIV/TB - o HIV- : 25% pts 25% HIV/AIDS pts - ART pts HIV/TB WHO Global Report 2014
  6. 6. HIV/TB: WHO Global Report 2014
  7. 7. HIV/TB: WHO Global Report 2014
  8. 8. ( 1 )
  9. 9. (ROIs) - lipoarabinomannan (LAM): scavenger - ( ATP )
  10. 10. TNFa ( , , NK cells) : RNIs (2-6wks)
  11. 11. CD4+ CD8+ INF,TNF CD8+ NRI
  12. 12. : NRI : TNF
  13. 13. H :
  14. 14. TNF (transmembrane TNF tmTNF) O tmTNF (soluble TNF sTNF) sTNF TNF
  15. 15. TNF- Lancet Infect Dis 2008;8:60111 Infect Immun.2001;69:1847-55 J Immunol.2002;168:4620-7 (C-C C-X-C) (VCAM, ICAM, E selectin) ( inducible NOS2) ,
  16. 16. NF Lancet Infect Dis 2008;8:6011 o Infliximab (REMICADE): IgG1 o Adalimumab (HUMIRA): o Certolizumab (CIMZIA): Fab o Etanercept (ENBREL): TNFR ( TNFR2 Fc IgG1)
  17. 17.
  18. 18. 1998-2001 70 TB infliximab 9 etanercept. NEJM2001;345(15):1098-104. , TB 5.8- 6.4:100,000 , infliximab 52.2-54:100,000 . 12 infliximab, infliximab 2-9 etanercept. Clin Infect Dis.2004;39:1254-5. TB infliximab 173:100,000 . , infliximab etanercept. Clin Infect Dis.2004;39:1254-5. , TNF-, anti-TNF .
  19. 19. , 1999-2005, infliximab, adalimumab etanercept, 18:1000, 23:1000 3:1000 . Acta Reumatol Port.2006;31:247-53. , RATIO 69 TB, , 36 infliximab 28 adalimumab, , . Arthritis Rheum.2009;60:1884-94. , infliximab adalimumab etanercept. Arthritis Rheum.2007 Jun 15;57(5):756-61. TB adalimumab infliximab.
  20. 20. sTNF ( ) tmTNF IFN etanercept sTNF tmTNF
  21. 21. anti-TNF : - - vs etarnecept H1 , - infliximab 80% NEJM2001;345(15):1098-104 adalimumab 62% AnnRheumDis2009;68:1863-1869
  22. 22. ( 45-50 IU/L: spec (+): 33% ( ): 70-90%
  23. 24. o Lymphadenopathy in a patient with primary tuberculosis: chest radiograph shows a bulky left hilum and a right paratracheal mass, findings that are consistent with lymphadenopathy and are typical in pediatric patients
  24. 25. Chest radiograph of an HIV-infected patient with tuberculosis shows a very large left-sided pleural effusion.
  25. 26. -
  26. 27. 1 : - 96% 40% - - (2/3), (1/3) - >2cm * - -
  27. 28. Ghon: - 1 - + LN - 15% 1 -
  28. 29. 1 >90% (LTBI) low grade 1 6 1 (LTBI) HIV(-) HIV(+) 10% 10% (5% 2 ) NEJM 345;3 2001
  29. 30. LTBI HIV (predn 15mg/d 1mo) , , , bypass .
  30. 31. 1. 2. 3.
  31. 32. : - , - : , , , , , , . 10-40% - , , - 50-80% AIDS anti-TNF
  32. 33. ( LTBI) : - ( ) 20-50% ( ) () - , , , tree-in-budd ( : )
  33. 34. o Parenchymal postprimary tuberculosis: chest radiograph demonstrates the characteristic bilateral upper lobe fibrosis associated with postprimary tuberculosis.
  34. 35. Bilateral infiltrates (right greater than left) without evidence of cavitation
  35. 36. Extensive infiltrates with evidence of cavitation in the right upper lobe
  36. 37. o Parenchymal postprimary tuberculosis: high-resolution CT scan shows the typical apical cavitation of postprimary tuberculosis, with consolidation, nodules and tree in bud
  37. 38. Postprimary active tuberculosis in a 34-year-old man with weight loss and a chronic cough.(a)High-resolution CT scan of the left lung shows a thick-walled cavity and multiple peripheral small nodules and branching linear structures (arrows)
  38. 39. Parenchymal postprimary tuberculosis: high-resolution CT scan demonstrates multiple small, centrilobular nodules connected to linear branching opacities. This so-called tree-in-bud appearance is typically seen in postprimary tuberculosis.
  39. 40. Postprimary active tuberculosis in a 66-year-old woman with a chronic cough. High-resolution CT scans of the right lung show peripheral, poorly defined, small (24-mm-diameter) centrilobular nodules and branching linear opacities of similar caliber originating from a single stalk (the tree-in-bud pattern)
  40. 41. x3 Z-N smear 65% culture- positive 35% culture- positive (+) (-) PCR 1 . /a L Z-N smear (+) (-) ELISpot 90% sens, 80% spec /a/ * 30- 40% smear-negative TB * / 15%
  41. 42. iel-ielsen : - - (, ) / (17% ) /
  42. 43. CAP (CAP) (4wks ( 6 mo) hrs-days >2wks (patient delay 3- 4wks, healthcare delay 5-6wks) WBC 1-2wks) - , , - (III, IV, VI, VII) - - 5-1000/l 30-90% - 100-1000mg/dl - - - o , , , Willis,
  43. 61. Contrast-enhanced T1-weighted axial magnetic resonance imaging showed diffuse, thick, and sometimes nodular enhancement of the basal meninges (arrows), presumably due to inflammation. These findings are highly suggestive of tuberculous meningitis, but may also be observed in patients with: sarcoidosis, Wegener's granulomatosis, fungal meningitis, or chronic meningitis due to nocardia or actinomyces N Engl J Med 1999; 341:1197
  44. 62. Axial contrast-enhanced T1-weighted magnetic resonance (MR) image shows florid meningeal enhancement that is most pronounced within the basal cisterns
  45. 63. (tuberculomas): - - - - - : noncaseating, caseating with solid center, caseating with liquid center - wks-mos - o : , , , , , , , , ,
  46. 64. Contrast-enhanced CT scan shows multiple bilateral ring-enhancing lesions (tuberculomas) in the frontal and parietal lobes. Axial contrast-enhanced T1-weighted MR image demonstrates multiple enhancing caseating and non-caseating tuberculomas, predominantly within the left frontal and parietal lobes
  47. 65. HIV: - LTBI 10% - 2-3 35-40% o CD4+ >350/l: ( ) o CD4+