Tuberculosis Noon Conference 2007

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TB noon conference

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  • Tuberculosis Noon Conference 2007

    1. 1. Tuberculosis Miguel G. Madariaga, MD Assistant Professor of Medicine University of Nebraska Medical Center
    2. 2. Tuberculosis: an ancient scourge Lombardi, Rev Antropol Chil, 2000.
    3. 3. Famous people with tuberculosis *Those who died from tuberculosis
    4. 4. Tuberculosis : the myth
    5. 5. The last 150 years in the history of tuberculosis
    6. 6. Tuberculosis: the epidemiological chain
    7. 7. Phylogenetic tree of Mycobacterium <ul><li>The M. tuberculosis complex </li></ul><ul><ul><li>M. tuberculosis </li></ul></ul><ul><ul><li>M. bovis </li></ul></ul><ul><ul><li>M. africanum </li></ul></ul><ul><ul><li>M. microti </li></ul></ul><ul><ul><li>M. caneti </li></ul></ul>
    8. 8. M. tuberculosis cell wall
    9. 9. The host
    10. 10. Tuberculosis transmission
    11. 11. Tuberculosis: the global picture
    12. 12. The impact of HIV on TB
    13. 13. The Kwa-Zulu Natal outbreak
    14. 14. Extensively drug resistant tuberculosis XDR TB is the occurrence of TB in persons whose M. tuberculosis isolates are resistant to isoniazid and rifampin plus resistant to any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin). CDC.
    15. 15. Causes for the increase of tuberculosis in the world <ul><li>Poor or no application of tuberculosis control programs </li></ul><ul><li>Poverty and the widening gap between the rich and the poor </li></ul><ul><li>Massive immigration from tuberculosis endemic zones </li></ul><ul><li>The demographic explosion </li></ul><ul><li>The HIV epidemics </li></ul>
    16. 16. Pathogenesis of tuberculosis
    17. 17. The natural history and spectrum of tuberculosis
    18. 18. Primary pulmonary tuberculosis
    19. 19. Post-primary tuberculosis
    20. 20. Pathology of tuberculosis
    21. 21. Pulmonary tuberculosis in HIV <ul><li>Those with higher CD4 cell counts (>400/mm3) present similarly to those without HIV, with upper lobe cavitary disease and a low risk of extrapulmonary dissemination </li></ul><ul><li>At more advanced stages of immunosuppression, patients are more likely to have disseminated disease and unusual pulmonary manifestations such as mediastinal-hilar adenopathy, focal lower lobe or diffuse interstitial infiltrates, and pleural effusions. </li></ul><ul><li>In these cases, sputum acid-fast smears are less likely to be positive than those with cavitary disease </li></ul>
    22. 22. Pleural tuberculosis Adenosine deaminase in pleural fluid
    23. 23. Lymph node tuberculosis
    24. 24. Genitourinary tuberculosis
    25. 25. Bone and joint tuberculosis
    26. 26. Peritoneal and digestive tract tuberculosis
    27. 27. Cerebral and meningeal tuberculosis
    28. 28. Miliary tuberculosis
    29. 29. The tuberculin skin test
    30. 30. Criteria for a positive TST
    31. 31. False positive and false negative results for TST
    32. 32. The booster effect in the elderly
    33. 33. Interferon gamma assays (QuantiFERON TB-Gold)
    34. 34. Advantages and disadvantages of gamma interferon based assays <ul><li>Sensitivity similar to TST </li></ul><ul><li>Less likely to be positive in past exposure to BCG or atypical mycobacteria </li></ul><ul><li>Only one patient visit </li></ul><ul><li>Does not cause booster phenomenon </li></ul><ul><li>Less subject to reader bias and error </li></ul><ul><li>As with the TST, additional tests are needed to exclude TB disease and confirm LTBI. </li></ul><ul><li>Blood samples must be processed within 12 hours of blood draw. </li></ul><ul><li>High cost </li></ul><ul><li>Requires special instruments </li></ul>
    35. 35. Getting a sputum sample
    36. 36. Ziehl-Nielsen stain
    37. 37. Culture
    38. 38. Radiology
    39. 39. Histopathological diagnosis
    40. 40. Fluorochrome staining (auramine)
    41. 41. New mycobacterial culture methods <ul><li>BACTEC (liquid media) </li></ul><ul><li>Advantages </li></ul><ul><ul><li>Time saving. Drug susceptibility in 3-6 days. </li></ul></ul><ul><ul><li>Increased sensitivity </li></ul></ul><ul><ul><li>ID and drug susceptibility without subculturing </li></ul></ul><ul><li>Disadvantages </li></ul><ul><ul><li>Needs radioisotopes. </li></ul></ul><ul><ul><li>High cost </li></ul></ul><ul><ul><li>Risk of cross contamination </li></ul></ul><ul><ul><li>Laborious performance </li></ul></ul><ul><li>There is non-radiometric BACTEC! </li></ul><ul><li>Non-radiometric biphasic culture media (MB-Septi-Check) </li></ul><ul><ul><li>Greater sensitivity, but slow growth </li></ul></ul><ul><li>AFB blood cultures </li></ul><ul><ul><li>Based on the lysis-centrifugation principle in the radiometric system, or on the new automated culture systems. </li></ul></ul><ul><ul><li>Use is indicated in AIDS patients with CD4+ < 50 </li></ul></ul>
    42. 42. Microscopic observation broth-drug susceptibility assay (MODS)
    43. 43. New techniques for identifying Mycobacteria <ul><li>NAP test in Bactec </li></ul><ul><li>Chromatography </li></ul><ul><li>Genetic probes </li></ul><ul><li>Polymerase chain reaction (PCR) </li></ul><ul><ul><li>Amplification with primers, followed by detection of a specific fragment via electrophoresis. </li></ul></ul><ul><ul><li>Amplification of a DNA fragment common to all mycobacterial species, followed by recognition with species-specific probes. </li></ul></ul><ul><ul><li>Amplification of a DNA fragment common to all mycobacterial species, followed by lysis of the product with restriction enzymes, and visualisation of the restriction fragments in agarose gel (PCR with restriction fragment length polymorphism analysis) </li></ul></ul>
    44. 44. Prevention of resistance: the need for drug combinations
    45. 45. The need for prolonged treatments: bacillary populations of M. tuberculosis <ul><li>Metabolically active and under conditions of continuous growth </li></ul><ul><li>Bacilli in the acid-inhibition phase </li></ul><ul><li>Bacilli in the sporadic multiplication phase </li></ul><ul><li>Persistent or totally dormant populations </li></ul>
    46. 46. Treatment algorithm for tuberculosis
    47. 47. Approved combinations for the treatment of tuberculosis
    48. 48. First line TB drugs
    49. 49. Adverse reactions of first line drugs
    50. 50. Adverse reactions of first line drugs
    51. 51. Other treatment considerations <ul><li>No differences in the treatment of extrapulmonary TB versus pulmonary TB. </li></ul><ul><li>Corticoid treatment only in : meningeal TB, miliary TB, and pericardial TB. </li></ul><ul><li>Surgery only for managing the sequelae or complications of pulmonary TB, and in very exceptional cases of multidrug-resistant TB. </li></ul><ul><li>Re-treatment may be required due to pharmacological failure, patient abandonment, or poor adherence to therapy (make sure no resistance) </li></ul><ul><li>If resistance use at least 2 and preferably 3 drugs that the patient has never used </li></ul>
    52. 52. Guidelines for TB retreatment
    53. 53. Antituberculosis agents available in US
    54. 54. Priority situations for the use of DOT
    55. 55. NNRTIs/TB meds: interactions
    56. 56. PIs/TB meds: interactions
    57. 57. Future treatment options <ul><li>Antibiotics: rifamycin derivatives, fluoroquinolones, macrolides, oxazolidinones, nitroimidazoles </li></ul><ul><li>Non-antibiotics that inhibit mycobacterial growth </li></ul><ul><li>Substances that interfere with the biosynthesis of vital components of mycobacteria </li></ul><ul><li>Resensitizing agents </li></ul><ul><li>Immunotherapy </li></ul><ul><li>Liposomal antibiotics? </li></ul><ul><li>Nanotechnology? </li></ul>
    58. 58. Bacillus Calmette-Guerin vaccine <ul><li>BCG is an attenuated M. bovis strain. </li></ul><ul><li>It interferes with tuberculin test. </li></ul><ul><li>It protects mainly against the meningeal and disseminated forms of disease   </li></ul><ul><li>It is widely used in the world except in the USA </li></ul><ul><li>Contraindicated in HIV </li></ul>
    59. 59. Infection control
    60. 60. Treatment of latent tuberculosis
    61. 61. Key issues in the treatment of latent TB <ul><li>Rule out active disease (no symptoms, negative CXR) </li></ul><ul><li>Consider baseline LFTs and HIV test </li></ul><ul><li>No need to monitor monthly enzymes unless patients are at risk (hepatitis, other potentially hepatotoxic drugs, too old) </li></ul><ul><li>Consider vitamin B6 supplement </li></ul><ul><li>9 months of INH best, 6 OK. </li></ul>
    62. 62. Tuberculosis in Nebraska
    63. 63. Tuberculosis in Nebraska <ul><li>Tuberculosis Program Manager </li></ul><ul><li>Pat Infield, RN </li></ul><ul><li>301 Centennial Mall </li></ul><ul><li>P.O. Box 95007 </li></ul><ul><li>Lincoln, NE 68509-5007 </li></ul><ul><li>(phone) 402.471.6441 </li></ul><ul><li>OneWorld Community Health Centers 4920 South 30th Street • Suite 103 • Omaha, NE 68107 </li></ul><ul><li>Monthly clinic. Second Thursday 6-8 pm </li></ul>

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