1. Tuberculosis
ד"ר מנדל גלזר מנהל מכון רוקח ומלש"ח ירושלים שירותי בריאות כללית, מחוז ירושלים מסונף לאוניברסיטה העברית מכון הריאה ב"ח הדסה ע"כ

2. מלש"ח – מרכז לאבחון וטיפול בשחפת
9 מלש"חים בארץ
לשכות הבריאות האזוריות
ירושלים – מרכז רוקח

3. מרכז רפואי על שם ד"ר י.ל. רוקח

4. מלש"ח מרפאות קהילה מלש"חים אחרים לשכת הבריאות משרד הבריאות בתי חולים
כלליים
מלש"ח
צה"ל
בי"ח
ספציפיים
מרכז
קליטה
מבוטחי כל
הקופות
עובדים זרים

5. History Terms Consumption Phthisis [ Greek ] Phthisis Pulmonalis
Scropula
Tabes Mesenterica
Koch’s Disease

6. TB History
1020 – Ibn Sina [ Avicena ] described in first as contagious disease
Senabsin - name Tuberculosis
1859 – First sanatorium in Germany
1882 – R.Koch found bacilli
1905 – Nobel Price
1906 – A. Galmette and Camele Gurien – first immunisation

7. TB History 1907 – National TB Association founded in US and Canada
– First human vaccination used in France
– Streptomycin was developed
80’s – Drug resistance appeared
The 20th _ TB kill’s more than 100 million people

8. Incidence 8,8 million new cases and 1,4 million died in 2010.
19-43% of the world`s population are
infected by M.Tuberculosis.
>95% of cases occur in developing
countries.

12. TB - USA

15. Tuberculosis . Infectious disease caused by Mycobacterium Tuberculosis
Transmitted from a person with active lung disease
Airborne transmission
Exposure time, host susceptibility dependant

16. MT COMPLEX . Mycobacterium Tuberculosis Mycobacterium Bovis
Mycobacterium Africanum
M.Microti, M.Pinnipedii, M.Carpae

17. MTB Small rod-like bacillus Aerobic Divides every 16-20 hours
Can identify under regular microscopy
Ziehl-Neelsen stain
Fluorescent microscopy
Rhodamine, Ahramine stain

18. Mycobacterium TB

19. Sputum ZN Stained

20. TB

22. Tuberculosis
Active Disease
Latent [ LTI ]

23. Tuberculosis MDR [ Multi drug resistance ]- Rifampicin, Isoniazid
XDR [ Extensive drug resistance ] – Rif., Ison., Fluoroqinolones, Aminoglicosides
HIV

30. Lung TB

43. TB Diagnostics Sputum Bronchoscopes Gastric Aspiration
Histopathology [ Biopsy ]

44. Rapid TB Tests NAA [ Nucleic Acid Amplification ] Gen-Probe MTD
Enhanced MTD
Amplicor MT Test

46. TB in Children
Under 5year triad of close contact, positive TST, suggestive findings on the x-ray [ primary complex, opacification with hilar or subcarinal lymphadenopathy ] or physical examination are useful for diagnosis for active TB
Gastric aspiration

48. Relative Risk for TB AIDS 110- 170 HIV 50 - 110 Transplant 20 - 74
CA Head/Neck
TNF Inhibitor ,7 – 9
Solitary Granuloma
Apical Fibronodules
Resent TB Inf [ under 2 years ] 15

49. Relative Risk for TB CRF – Hemodialysis 10-25 Silicosis 30
Anti – TNF ,7 - 9
Young age [under 5 ] ,2 - 5
Glucocorticoids ,9
DM all types – 3,6
Smoker 1 p/d – 3
Underweight [ 85% ]

50. Close Contact - Disease Risk
Under 1 year old %
1 - 2 years % – 25%
2 – 5 years %
5 – 10 years %
Adolescent , young adults 10% - 20%
Other adults % - 5%

51. LTI Diagnosis TST Interferon-Gamma release assay [IGRA ]:
Enzyme-linked immunosorbent assay - Quantiferon e.g. Elisa
Enzyme-linked immunospot assay – Elipsot e.g. T-Spot TB assay.

52. Tuberculin test (Mantoux)
Intradermal injection of 5 TU (tuberculin units) of purified protein derivative (PPD).
Induration measured after hours.
Booster [ two step testing ]
Conversion: an increase of 6-10mm to >10mm.

53. Booster Response, Conversion
Booster – 10mm or more and has increased by 6mm since the previous in the absence of exposure. Lover risk than initial positive TST
Conversion – 10mm or more and has increased by 6mm since the previous up to 8weks after initial negative TST in the setting of recent exposure
Reaction 10 and more mm should be referred for medical evaluation to exclude active TB

54. TST

57. התפלגות תוצאות PPD אצל ילידי ישראל

58. Close Contact PPD Negative – Second test should
undergo 8 – 12 weeks later

60. Potential causes of false negative Tuberculin test : Technical - correctible
Tuberculin material : improper storage [ exposure to light, heat ], contamination, improper dilution, chemical denaturation
Administration: injection of too little tuberculin, or too deeply, or more than 20 minutes after drawing up into the syringe
Reading: inexperienced or biased reader, error in recording

61. Potential causes of false negative tuberculin tests: Biologic – not correctible
Infections: Active TB [ especially if advanced ], bacterial infections
[ typhoid fever, brucellosis, typhus, leprosy, pertussis ]. HIV inf
[ especially if CD count less than 200 ], viral infection [ measles, mumps, varicella ], fungal infection [ blastomycosis ]
Live virus vaccination : measles, mumps, polio
Immunosuppressive drugs : corticosteroids, TNF inhibit, others
Metabolic disease: CRF, severe malnutrition, stress [ surgery, burns ]
Diseases of lymphoid organs: Lymphoma, CLL, Sarcoidosis
Age under 6 months, elderly

63. LTI Diagnosis IGRAs Specificity 95%, Sensitivity 80-90%
TST - Specificity 97% in non BCG, and 60% in BCG administered, Sensitivity -80%
IGRAs sensitivity is diminished in HIV with lower CD4 [ TSPOT is less affected ]
M.Kansasii, M.Marinum affect

64. LTI Diagnosis USA – IGRAs used, but not in addition to TST
Canada – IGRAs is appropriated in the setting of negative TST
UK – TST is the first-line test. If positive – may be considered IGRA depending of BCG status

66. TB - TREATMENT
DOT [ Direct Observed Therapy ]

67. TB Treatment First Line [ INH, RIF, ETH, PZM, Rifabutin]
Second Line [ Cycloserine, Ethionamide, Streptomycin, Amikacin, Kanamycin, Capreomycin, PAS, Levofloxacin, Moxyfloxcin ]
New drugs [ Interferon, Linezolid ]
Surgery

74. Active TB - Treatment Prolonged Treatment in cavitary , miliary TB
In pericarditis, meningitis – corticosteroids
Treatment failure – positive sputum culture after 4months treatment - continue 4 drug regimen

76. Rifampicin 4 months; children 6 months.
Treatment Regimes for LTBI
Isoniazid 6 to 9 months.
Rifampicin 4 months; children 6 months.
Rifampicin + Isoniazid 3 months.
Liver and kidney functions monitoring.

78. Risk of Isoniazid-Induced Hepatitis
More than 65 years - more than 5%
50 – 65 years %
Less 50 years – less than 3%
Less than 35years – less than 1%

79. BCG Benefits: diminished risk of TB meningitis
Reaction 3-19mm in the first 3 months, after less than 10mm
Should not be administrated in individuals with immune compromise

80. BCG
לילודים ולילדים ממשפחות עולים חדשים ותושבים שאינם אזרחי ישראל המגיעים מארצות בהן שכיחות TB גבוה
מייד אחרי לידה ועד גיל 4 [ שלא חוסן או שאין עדות על החיסון וכשHIV נשלל ]

81. BCG Adverse Events - 5% Fever - 2,9% Signif. Proteinurua - 1%
Granulomatous Prostatitis ,9%
Pneumonitis ,7%
Granulomatous Hepatitis ,7%
Artralgia ,5%
Epididymitis ,4%
Cystitis

82. BCG – Adverse Events Sepsis - 0,4% Rash - 0,3%
Uretral Obstruction ,3%
Contracted Bladder ,2%
Renal Abscess ,1%
Cytopenia ,1%
Osteomyelitis

83. NTM Infection MAC M. Kansasii
Rapidly Growing – M.Fortuitum, M.Abscessus, M.Chelonae

84. תודה