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
TB History 1907 – National TB Association founded in US and Canada 1921 – First human vaccination used in France 1946 – Streptomycin was developed 80s – Drug resistance appeared The 20 th _ TB kills more than 100 million people
Incidence -8,8 million new cases and 1,4 million died in % 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
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 HIV Transplant CA Head/Neck 16 TNF Inhibitor 1,7 – 9 Solitary Granuloma 2 Apical Fibronodules Resent TB Inf [ under 2 years ] 15
Relative Risk for TB CRF – Hemodialysis 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% years 12% – 25% 2 – 5 years 5% 5 – 10 years 2% Adolescent, young adults 10% - 20% Other adults 3% - 5%
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.
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
התפלגות תוצאות PPD אצל ילידי ישראל
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 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
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 מארצות בהן שכיחות TB גבוה מייד אחרי לידה ועד גיל 4 [ שלא חוסן או שאין עדות על החיסון וכש HIV נשלל ]