Tuberculosis ד"ר מנדל גלזר מנהל מכון רוקח ומלש"ח ירושלים...

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

TST

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