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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
מלש"ח – מרכז לאבחון וטיפול בשחפת
•9 " בארץ חים מלשהאזוריות • הבריאות לשכותרוקח – • מרכז ירושלים
מרכז רפואי על שם ד"ר י.ל. רוקח
מלש"ח
מרפאות קהילה
מלש"חים אחרים
לשכת הבריאות
משרד הבריאות
צה"ל
מבוטחי כלעובדים זריםהקופות
מרכז קליטה
בתי חוליםכלליים
בי"חספציפיים
History Terms
• Consumption• Phthisis [ Greek ]• Phthisis Pulmonalis• Scropula• Tabes Mesenterica• Koch’s Disease
TB History
• 1020 – Ibn Sina [ Avicena ] described in first as contagious disease
• 1839 - Senabsin - name Tuberculosis • 1859 – First sanatorium in Germany • 1882 – R.Koch found bacilli • 1905 – Nobel Price
1906 – A. Galmette and Camele Gurien – first immunisation
TB History
• 1907 – National TB Association founded in US and Canada
• 1921 – First human vaccination used in France
• 1946 – Streptomycin was developed • 80’s – Drug resistance appeared • The 20th _ TB kill’s more than 100 million
people
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.
TB - USA
Tuberculosis
. Infectious disease caused by Mycobacterium Tuberculosis
• Transmitted from a person with active lung disease
• Airborne transmission• Exposure time, host susceptibility dependant
MT COMPLEX
. Mycobacterium Tuberculosis• Mycobacterium Bovis• Mycobacterium Africanum• M.Microti, M.Pinnipedii, M.Carpae
MTB• Small rod-like bacillus• Aerobic• Divides every 16-20 hours• Can identify under regular microscopy• Ziehl-Neelsen stain• Fluorescent microscopy• Rhodamine, Ahramine stain
Mycobacterium TB
Sputum ZN Stained
TB
Tuberculosis
• Active Disease• Latent [ LTI ]
Tuberculosis
• MDR [ Multi drug resistance ]- Rifampicin, Isoniazid
• XDR [ Extensive drug resistance ] – Rif., Ison., Fluoroqinolones, Aminoglicosides
• HIV
Lung TB
TB Diagnostics
• Sputum • Bronchoscopes• Gastric Aspiration• Histopathology [ Biopsy ]
Rapid TB Tests
• NAA [ Nucleic Acid Amplification ]• Gen-Probe MTD• Enhanced MTD• Amplicor MT Test
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
Relative Risk for TB
• AIDS 110- 170• HIV 50 - 110• Transplant 20 - 74• CA Head/Neck 16• TNF Inhibitor 1,7 – 9• Solitary Granuloma 2• Apical Fibronodules 6 - 19• Resent TB Inf [ under 2 years ] 15
Relative Risk for TB
• CRF – Hemodialysis 10-25• Silicosis 30• Anti – TNF 1,7 - 9 • Young age [under 5 ] 2,2 - 5• Glucocorticoids 4,9• DM all types 2 – 3,6• Smoker 1 p/d 2 – 3• Underweight [ 85% ] 2 - 3
Close Contact - Disease Risk
• Under 1 year old 50%• 1 - 2 years 12% – 25%• 2 – 5 years 5%• 5 – 10 years 2%• Adolescent , young adults 10% - 20%• Other adults 3% - 5%
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.
Tuberculin test (Mantoux)
• Intradermal injection of 5 TU (tuberculin units) of purified protein derivative (PPD).
• Induration measured after 48-72 hours.• Booster [ two step testing ]• Conversion: an increase of 6-10mm to
>10mm.
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
אצל ילידי ישראלPPDהתפלגות תוצאות
0.0%
10.0%
20.0%
30.0%
40.0%
50.0%
60.0%
70.0%
לא ידוע+00-55-1010-1515
2008 2009 2010
Close Contact
• PPD Negative – Second test should undergo 8 – 12 weeks later
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
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
Potential causes of false negative tuberculin tests: Biologic – not correctible
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
LTI Diagnosis
USA – IGRAs used, but not in addition to TSTCanada – IGRAs is appropriated in the setting of
negative TSTUK – TST is the first-line test. If positive – may be
considered IGRA depending of BCG status
TB - TREATMENT
• DOT [ Direct Observed Therapy ]
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
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
Treatment Regimes for LTBI
Isoniazid 6 to 9 months.
Rifampicin 4 months; children 6 months.
Rifampicin + Isoniazid 3 months.
Liver and kidney functions monitoring.
Risk of Isoniazid-Induced Hepatitis
• More than 65 years - more than 5%
• 50 – 65 years - 3-5%
• Less 50 years – less than 3%
• Less than 35years – less than 1%
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
BCG
לילודים ולילדים ממשפחות עולים חדשים •ותושבים שאינם אזרחי ישראל המגיעים
גבוהTBמארצות בהן שכיחות [ שלא חוסן או שאין 4מייד אחרי לידה ועד גיל •
נשלל ]HIVעדות על החיסון וכש
BCG Adverse Events - 5%• Fever - 2,9%• Signif. Proteinurua - 1%• Granulomatous Prostatitis - 0,9%• Pneumonitis - 0,7%• Granulomatous Hepatitis - 0,7%• Artralgia - 0,5%• Epididymitis - 0,4%• Cystitis
BCG – Adverse Events
• Sepsis - 0,4%• Rash - 0,3%• Uretral Obstruction - 0,3%• Contracted Bladder - 0,2%• Renal Abscess - 0,1%• Cytopenia - 0,1%• Osteomyelitis
NTM Infection
• MAC• M. Kansasii• Rapidly Growing – M.Fortuitum, M.Abscessus,
M.Chelonae
