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

http://upload.wikimedia.org/wikipedia/commons/5/58/Pulmonary_tuberculosis_symptoms.png

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