1. 10-28-a
    • Tb Disease Clinical Features
    • “The Consumption”:
    • Fever, weight loss/wasting
    • Night sweats
    • Malaise, anorexia
    • Cough > 2wks; classically with bloody sputum
    • Chest pain, often pleuritic
    • Variable, and may be more subtle! Esp in the elderly, young, and HIV(+)
  2. Laboratory in Tb disease
    • Results non specific, don’t help much
    • Anemia (normochromic), hypoalbuminemia late
    • Late evidence of SIADH, adrenal insufficiency
  3. CXR
    • Will have great lymphadinopathy in the hylum
    • Miliary Tb – “millet seeds” lungs are receding
    • HIV(+) Patient, elderly patient, not a regular picture – see diffuse infiltrates – might not be just pneumocyctis, might be just Tb
  4. Extrapulmonary Disease
    • Hematogenous phase early in infection
    • “Common sites”:
    • CNS – acute or chronic meningitis, brain abscess
    • Kidney – one cause of “sterile” pyuria
    • Adrenal glands – Addison’s Disease
    • Liver – granulomatous hepatitis
    • Bone – Spondylitis – classically described Pott’s Disease, long bones
    • Serosa – pleura, pericardium, peritoneum
    • Most often without active pulmonary disease!!:
  5. Tb Disease Dx
    • Index of suspicion!
    • Growth of MTB is definitive
    • AFB (or fluorochrome) stained sputum smear is the most rapid method to detect presumptive MTB: fast, BUT sensitivity is only 50-70%
    • So when negative, doesn’t rule disease out.
    • Sensitivity of AFB smears of “fluids” such as CSF, urine, etc. are <30%
  6. Tb Dx Caveats
    • -‘ve AFB smear does not exclude TB!
    • BUT +’ve sputum AFB smear in a patient with suggestive illness has PPV of 90%
    • Yield of culture varies with AFB load: 3 specimens over 24-72 hous, esp one in the early morning
    • Growning role for NAAT: especially in CSF and other “fluids”; direct test on sputum, best if AFB(+)
    • NO role for skin testing in active disease!!: On EXAM!
  7. Tb RX
    • Populations of MTB in patient with active TB – different stages
    • “Rapidly” growing bacilli: – usually in cavities –
    • “Slowly” or “Intermittently” growing bacilli: – usually in the acid environment of necrosis, some are intracellular, some are extracellular
    • 2 phases of therapy:
    • Initial rapid killing of large number of bacilli (rapidly growing)
    • Longer phase during which bacilli with slower growth rate are killed “sterilizing phase or continuation phase
  8. Tb Rx different phases, different activities
    • Early Activity: rate of killing is fastest – need to try to kill as many as we can, want to achieve –‘ve or decreased AFB
    • Sterilizing activity: Kill viable bacilli that are growing slowly or intermittently to minimize the risk of relapse
    • Measure: rate of positive sputum AFB cultures after 2mo of Rx or relapse rate after Rx comopleted
    • So the better the sterilizing activity is, the shorter the treatment duration
  9. TB First line Rx
    • Drug abbreviation Early activity Sterilizing activity
    • Isonazid INH +++ +
    • Rifampin RIF + +++
    • Pyrazinamide PZA ++ +++
    • Ethambutol EMB ++ 0
    • Streptomycin **** SM + 0
  10. Look at the poster drugs slide that Lesse will post!!!!
  11. TB Rx – Resistance
    • Deveolopment of resistance:
    • patient non-compliance – directly observed therapy
    • Inappropriate prescription – wrong or too few drugs
    • Spontaneous mutation – 1 in 10^5-10^8
    • Resistance phenotypes:
    • Single drug
    • Multiple drug
  12. Current Rx Scheme for Tb
    • Start INH+RIF+PZA+EMBx2 months
    • If bug INH and RIF susceptible, continue 4 more months
    • discontinue PZA & EMB
    • Basic principles: multiple drugs – avoid resistance, bactericidal, long course
  13. Current Tb Rx scheme problem:
    • LIVER DYSFUNCTION: jaundice, elevated blood tests
    • Discontinue all Rx
    • Re-add one at a time and monitor liver toxicity.
  14. Identifying Tb infection
    • Treating those that are infected, but don’t show signs of clinical Tb
    • Stick to screening high risk populations, not low-risk persons
  15. Targeted Tuberculin Testing
    Focuses tuberculin skin testing (TST) on high-risk groups rather than everyone
  16. Latent TB infection (LTBI)
    • Person with a +’ve TST with no evidence of active disease
    • Rx: replaces the older terms “preventive therapy” and “chemoprophylaxis”
  17. Tuberculin skin testing
    • PPD 0.1 ml injected intradermally
    • Measure amount of INDURATION at 48-72 hrs
    • Don’t need to look at erythema, don’t need to write it down either, just look at induration – the palpable lump!
  18. Criteria for TST positivity
    • Some soil NTM immunologically cross-react with MTB
    • Cut-off for +’ve TST range from 5-15 mm depending on Tb risk
    • >/= 15 mm (for those with no/low Tb risk)
    • >/= 10 mm recent immigrants <5yrs, residents workers of high-risk congregate settings
    • Persons with certain clinical exposures
    • >/= 5 mm HIV infection, recent contacts of a known Tb case, organ transplants, etc.
    • measure the longest diameter
  19. PPD Reactor definition
    • Positive PPD of unknown duration
    • No prior testing or prior test results not known
  20. PPD Converter definition
    • Person with negative PPD reaction who on repeat testing has an increase in reaction size of >/= 10 mm within a 2-year period
    • High risk of developing active Tb, and these are the people we really want to track down
    • Greatest risk of developing active Tb in 2 years
  21. False Negative PPD reasons
    • Anergy
    • Recent of overwhelming TB
    • Recent immunization with live virus vaccines(s)
    • Recent viral infection: measles, chickenpox
  22. PPD alternative
    • $185, interferon gamma release assay (IGRA)
    • particularly useful in people who have received BCG vaccine
  23. BCG Vaccine & TST
    • PPD reactivity wanes over time after BCG vaccination
    • PPD testing can boost the immune response
    • Those with prior BCG vaccine should have TST done if indicated
    • However, >/= 20 mm induration unusual with BCG
  24. Treatment regiment for LTBI
    • INH 300 mg daily for 9 mos – preferred
    • INH 600 mg 2x.wk – alternative
    • RIF 300 mg daily for 4 months – alternative, especially if evidence of INH resistance
  25. Non-tuberculous mycobacteria – recognize that they exist
    • M.marinum: fish tak granuloma or pond granuloma, cutaneous lesions, typical history – treat with tetracyclene
    • M. Ulcerans: Buruli ulcer in the tropics, severe skin ulceration, bone involvement, can lead to secondary infections
    • M. kansasii: soil origin, no person-to-person transmission; the most TB-like of all the NTM/MOTT
    • M. scrofulaceum: Scofula – lymphadenitis in children
    • M. gordonae: generally a contaminant, “tap water bacillus”
    • M. avium complex (MAC): severe disease in HIV
    • M. Fortuitum complex: may cause local infection in normal or compromised host
  26. Leprosy
    • 4.2 million cases in the world
    • 95% of population MAY be immune
    • Cardinal findings: Infiltrative skin lesions, hypoesthesia, peripheral neuropathy
    • Tuberculoid: paucibacillary
    • Lepromatous: multibacillary
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