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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(+)
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Laboratory in Tb disease
- Results non specific, don’t help much
- Anemia (normochromic), hypoalbuminemia late
- Late evidence of SIADH, adrenal insufficiency
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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
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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!!:
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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%
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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!
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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
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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
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TB First line Rx
- Drug abbreviation Early activity Sterilizing activity
- Isonazid INH +++ +
- Rifampin RIF + +++
- Pyrazinamide PZA ++ +++
- Ethambutol EMB ++ 0
- Streptomycin **** SM + 0
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Look at the poster drugs slide that Lesse will post!!!!
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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
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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
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Current Tb Rx scheme problem:
- LIVER DYSFUNCTION: jaundice, elevated blood tests
- Discontinue all Rx
- Re-add one at a time and monitor liver toxicity.
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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
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Targeted Tuberculin Testing
Focuses tuberculin skin testing (TST) on high-risk groups rather than everyone
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Latent TB infection (LTBI)
- Person with a +’ve TST with no evidence of active disease
- Rx: replaces the older terms “preventive therapy” and “chemoprophylaxis”
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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!
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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
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PPD Reactor definition
- Positive PPD of unknown duration
- No prior testing or prior test results not known
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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
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False Negative PPD reasons
- Anergy
- Recent of overwhelming TB
- Recent immunization with live virus vaccines(s)
- Recent viral infection: measles, chickenpox
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PPD alternative
- $185, interferon gamma release assay (IGRA)
- particularly useful in people who have received BCG vaccine
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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
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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
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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
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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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