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Diagnostic Tests

Diagnostic Tests. Chest x-ray Patchy or nodular infiltrate Apical or sub-apical posterior aspects of UPPER LOBES (or superior segment of lower lobes) Cavity usually without an air-fluid level pneumonic lesion with enlarged hilar nodes consider primary TB. Clinical Manifestations.

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Diagnostic Tests

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  1. Diagnostic Tests • Chest x-ray • Patchy or nodular infiltrate • Apical or sub-apical posterior aspects of UPPER LOBES (or superior segment of lower lobes) • Cavity • usually without an air-fluid level • pneumonic lesion with enlarged hilar nodes • consider primary TB

  2. Clinical Manifestations • Pulmonary • Non-HIV: 85% • HIV+: • 38% pulmonary only • 30% extrapulmonary only • 32% pulmonary and extrapulmonary • X-ray findings

  3. Clinical Manifestations: Pulmonary TB • Coughing > sneezing, speaking • correlates with infectiousness • “The principal risk for acquiring infection with M.Tb. is breathing” Bloom and Murray, 1992 • Fever (about 80%), • Weight loss, malaise • Probably cytokine mediated

  4. Infectiousness of Source Case Transmission highly likely Less efficient transmission Non-cavitary disease Sputum AFB smear negative Not coughing Casual contact Outdoor contact very unlikely Cavitary disease: billions of bacilli Sputum AFB smear +++ Coughing (& sneezing & talking) Household contact

  5. Epidemiology: Who Gets TB? • Who gets TB infection? • Who gets TB disease? • Definitions: • TB infection: TB exposure that leads to local induration in response to intradermal injection of purified protein derivative (PPD) • TB disease = tuberculosis = active TB

  6. Who Gets TB infection? • In the world - ubiquitous • ~ 1/3 of the world’s population infected • 80% in developing countries • Immigrants from these other countries to U.S. • major source of recent increase in U.S. TB

  7. Who Gets TB infection in the U.S.? Exposure • medically underserved • urban (& in NC, rural) poor • minority populations** • Southeast Asian, African-American, Hispanic

  8. Annual Case Rates by Race/Ethnicity 1990 Annual New-case Rate per 100,000 in U.S. 42.6 in Asian/Pacific Islanders 33.0 in blacks 21.4 in Hispanics 18.9 in Native Americans 4.2 in U.S.-born whites 2/3 of cases occur in racial or ethnic minorities

  9. Laboratory • Processing: mucolysis, homogenization, bacterial contamination and concentration • Smear staining: • Ziehl-Neelsen acid-fast stain • auramine 0 fluorescence

  10. Laboratory • Reading the slide: • Examined an equivalent of 300 oil immersion fields = negative • Quantitated: 1-4+ or # bacilli/field • A positive smear = 5000-10,000 acid-fast bacilli/ml sputum • TB or non-TB mycobacterium???

  11. Making the Definitive Diagnosis • Smear: Auramine-rhodamine • Increased sensitivity • Confirmed by Ziehl-Neelson • AFB + does not = TB • at Duke, AFB+ smear is MOTT 2x >TB • at CMC, Charlotte, AFB+ smear is TB 5x > MOTT

  12. Making the Definitive Diagnosis • Cultures: Broth-based growth systems • average time to detection: • 10-18 days, e.g. BACTEC • 18-28 days, conventional • Susceptibilities: additional ~ 7 days • if not at Duke, always order on first specimen

  13. Expectations of TB Therapy: Pre-chemotherapy Era Therapy: • Improve nutrition • Bed rest and isolation, high altitude preferred • Surgical intervention in some Mortality rate at 5 years: 40-50%

  14. History of TB Therapy • 1940’s - Streptomycin [SM] • 1952: Isoniazid [INH] & p-aminosalacylic acid [PAS] • determined combination prevented rapid emergence of INH resistance • 1960’s: Rifampin [RIF], Pyrazinamide [PZA] & Ethambutol [EMB]

  15. History of TB Therapy • 1970-80’s: large clinical trials world-wide • 1977: 9 mos vs 18 mos INH, RIF, Streptomycin [SM] • Cure rates 95% in 9 mos • 1982: 6 mos total - 2 mos INH, RIF, PZA, SM, then drop PZA for last 4 mos • 1990: 6 mos INH, RIF, PZA (1st 2 mos) better than 9 mos INH & RIF [Cure rates 95%]

  16. Recommended Treatment Regimens: Rationale • INH during entire duration of Rx • < 6 months: unacceptably high failure rate • < 12 month regimens: must use INH and RIF, 2 mos at least • Initial PZA makes < 9 mos possible • Intermittent dosing (2-3 x/week) and daily dosing - equal efficacy

  17. Treatment Option 1 Option 2 Option 3 Daily INH, RIF, EMB or SM & PZA for 8 weeks, then INH & RIF for 16 weeks more (daily or 3x/wk DOT) (total 24 weeks) Daily INH, RIF, EMB or SM & PZA for 2 weeks, then Same drugs 2x/week for 6 weeks (DOT), then INH & RIF 2x/week for 16 weeks more (total 24 weeks) DOT 3x/week INH, RIF, EMB or SM & PZA (total 24 weeks) Start with Four Drug Therapy/DOT; TOTAL RX 6 months

  18. Expectations of TB Therapy: Post-chemotherapy Era • Therapy: • Specific, potent anti-tuberculous drugs in combination • Improve nutrition • Brief period of isolation • Success rate at 5 years: 95%

  19. Anti-TB Drugs: Resistance Naturally occurring mutations result in drug resistance at predictable rate: RIF: 1 in 108organisms INH,PZA,EMB,SM: 1 in 106organisms TB cavitary lesion has ~ 1 x 108 orgs IF INH alone, 100 orgs resistant on day 1

  20. 1. Patient non-compliance 2. Patient non-compliance 3. Patient non-compliance MDR-TB: Contributing Factors Antidote: Directly Observed Therapy MDR TUBERCULOSIS Immune deficiency (e.g., AIDS) Anti-tuberculous drugs available without prescription/management

  21. Other Management Issues • respiratory isolation while waiting • ID or pulmonary consultation • if sending home on TB meds: • contact county health department • before 4:45 Friday afternoon • request DOT

  22. Other Management Issues • Services available at North Carolina County Health Depts (vary state to state) • NC will provide all TB meds free to all people with TB, • plus DOT, • plus monitoring for symptoms, • plus contact tracing and testing, • plus nutritional support, housing and other support during therapy

  23. Relationship of HIV and TB Risk for M.TB-infected person (e.g., + PPD) to develop active TB HIV-seropositive: 7-10% ANNUAL risk HIV-seronegative: 10-15% LIFETIME risk Relative Risks HIV-infected - 113 fold increase AIDS - 170 fold increase Other IC* - 3.6-16 fold increase

  24. HIV positive steroid therapy/other IC High risk* recent conversion to +PPD 2.3% Risk of INH hepatitis Risk of active TB healthy, nl CXR, +PPD unk time 1.3% Unlikely* .1 35 yrs Age in Years +PPD skin test: when to give preventive therapy? *Risk categorized in Figure 1

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