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Tuberculosis Noon Conference 2007

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TB noon conference

TB noon conference

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Tuberculosis Noon Conference 2007 Tuberculosis Noon Conference 2007 Presentation Transcript

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