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NEW DIAGNOSTIC METHODS for TUBERCULOSIS

NEW DIAGNOSTIC METHODS for TUBERCULOSIS. Nural Kiper M.D. Professor of Pediatrics HacettepeUniversity Medical Faculty nkiper@hacettepe.edu.tr. Curr Opin Infect Dis 22:174–182 2009 . 2006 World Health Organization report over 9 million new cases and 1.7 million deaths

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NEW DIAGNOSTIC METHODS for TUBERCULOSIS

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  1. NEW DIAGNOSTIC METHODS for TUBERCULOSIS Nural Kiper M.D. Professor of Pediatrics HacettepeUniversity Medical Faculty nkiper@hacettepe.edu.tr

  2. Curr Opin Infect Dis 22:174–182 2009 2006 World HealthOrganization report over 9 million new cases and 1.7 million deaths Melissa R. Nyendaka, Deborah A. Lewinsohnb and David M. Lewinsohn

  3. Target DETECT of 70% of sputum+smearpatients & Successfully TREAT 85%

  4. NEW DIAGNOSTIC METHODS • Advances in microscopy • Advances in culture • Advances in nucleic acid amplification of Mycobacterium tuberculosis • Advances in detection of drug resistance • Advances in detection of latent tuberculosis • Biomarkers

  5. Advances in microscopy Smear microscopy-carbol fuchins,flourochromes Fluorecence microscopy LED technology(light emitting diode) Increased sensitivity -10%

  6. Advances in culture Lowenstein-Jensen(egg based solid media 4-6 hafta BACTEC,(liquid culture system) 1-3 hafta MGIT(mic.growth indicator tube) < 8days

  7. NAAT (nucleic acid amplification M. tuberculosis) CDC recommends first sputum all suspected Mtb patients FDA recommends smear +pulmonary diseases Gen-Probe Amp Mtb. Test Roche-Amplicor Test COBASA AmplicorBD-ProbeTec Direct test – Sens: 96% + , 66-72 %- Spesivity :+ 85 % , - 97 %) LAMP(Loop Mediated Isothermal Amplification) + 97-100% SENS ,- 99 % SPESIVITY

  8. Advances in the detection of drug resistance LiPAs(line probe assays)-NAAT- INNO-LiPARif.TB- GenoTypeMTBDR 82-100 % Sensitivy?? (73%) 100 % Spesivity MOODS(microscopic observation drug suscept) 95-100 ,low-cost,

  9. Advances in the detection of latent tuberculosis TST –tuberculin skin test TIGRA ESAT-6,CFP10 Quentiferon In-Tube,Gold ..whole-blood ELISA T-SPOT.TB….purified peripheral blood mononuclear cells enzyme-linked immunosopt

  10. TIGRA • Positive • Negative • Indeterminate(???) QFT-IT….0.35 (>spes,<sensi), T-SPOT.TB……4spot (-) …….5-7 spot (borderline)*risk??? ……..8-> spot (+)

  11. Clinical use of TIGRA • Severely immunocomprimised • Very young???

  12. BIOMARKERS • Very expensive • Ongoing trial

  13. UCUZ,GÜVENİLİR,UYGULANABİLİR TEST • 85% sensitivity • 97% spesivity • 392 000 deaths/annualy could be prevented(22% of global TB deaths) Nature 2006;444(Suppl 1)49-57

  14. Estimated proportion of children with TB is 3-13 % of all TB • In low-incame countries 15-40% • In Türkiye 3-6%, 2008(9%)

  15. Diagnosis of Tuberculosis in children • Clinical presentation • Positive history of contact with active TB • TST • Radiology • Bacteriology(30-40 % culture (10-15 % AFB • Histopathology

  16. Tuberculin skin test • Delayed hypersensitivity reaction, • 5TU PPD solution • Intradermal injection

  17. Reaction • 48-72 hours after injection • Induration is important

  18. LİSTERİA TİPİ CEVAP Indian J Pediatr 2007;74:641 KOCH TİPİ CEVAP

  19. PP-TB

  20. Prog P-TB

  21. C-TB C-TB R-TB

  22. Pleural TB Miliary TB

  23. DIAGNOSIS • Symptom-Based Approaches • Immune-Based Approaches • Bacteriology-Based Diagnosis • PCR-Based Tests Marais BJ Pediatric Pulmonology 2008;43:322

  24. Symptom-Based Approaches • Cough of >3 weeks persistent non-remitting cough • Failure to thrive > 3 months • Fatigue sensitivity 82.3% specificity 90.2% PPV 82.3% Pediatrics 2006

  25. Immune-Based Approaches MPB -4 Skin Test Transdermal application of MPB-64 Skin Patch Test 88-98%sensitivity 100 %specificty Scand Infect Dis 2001 ;33:405

  26. Bacteriology-Based Diagnosis Collection of bacteriologic specimens sputum fasting gastric aspirates • single hypertonic-saline induced sputum • nasopharyngeal aspirates • BAL Arch Dis Child 2007;92:693

  27. Summary • Family and medical history of patient, • Symptom-based approaches seemed to offer a practical solution in resource-limited region . • Radiological findings are also helpful for diagnosis • M.tuberculosis culture is more sensitive (30-40%)GS • TST & TIGRA’s fail to make the distinction between latent infection and active disease Paediatric Respiratory Reviews 2007;8:124 Marais JB,Madhukar P

  28. Summary • Family and medical history of patient, • Symptom-based approaches seemed to offer a practical solution in resource-limited region . • Radiological findings are also helpful for diagnosis • M.tuberculosis culture is more sensitive (30-40%)GS • TST & TIGRA’s fail to make the distinction between latent infection and active disease Paediatric Respiratory Reviews 2007;8:124 Marais JB,Madhukar P

  29. nkiper@hacettepe.edu.tr

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