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Tuberculosis

Tuberculosis. Chris Spitters, MD/MPH PHSKC TB Clinic. Objectives. Review basics of evaluation and initial management of TB suspects Describe relevant lab services for TB Describe local epidemiology and structure for working with PHSKC TB Control on TB cases

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Tuberculosis

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  1. Tuberculosis Chris Spitters, MD/MPH PHSKC TB Clinic

  2. Objectives • Review basics of evaluation and initial management of TB suspects • Describe relevant lab services for TB • Describe local epidemiology and structure for working with PHSKC TB Control on TB cases • Case studies touching on common problems in TB management

  3. Case 1 • 24 y/o Tibetan arrived 12 months ago • Cough, sputum, fever, night sweats, weight loss • No prior TB treatment history

  4. Criteria for Isolating Hospitalized TB Suspects and Cases • Pulmonary TB suspected and AFB smears (x 3)* pending or positive • Smears* negative but intend to treat for pulmonary TB and patient has received <2 weeks of therapy • Includes pleural TB suspects with negative smears and <2 weeks treatment • Following significant interruptions in treatment until smears negative and back on therapy x2 weeks *ideally qAMx3, but at least 8 hours apart

  5. Case 1--Laboratory Results • Sputum smear 4+ • Normocytic anemia (Hgb 9, MCV 81) • Albumin 2.8 • HIV negative • CBC/CMP otherwise negative • HBsAg neg, HCV neg

  6. Questions • Any further testing needed? • Should he be hospitalized? • Should treatment be started? • With what? • What else do you need to do?

  7. Baseline Diagnostic Examinations for TB • Chest x-ray • Sputum specimens • AFB smear, culture, and susceptibilities • nucleic acid amplification (MTD) • Extrapulmonary specimens • chemistry and cell count and cytology on fluids • Routine pathology • AFB stain/smear and culture • PCR • Special studies: ADA, molecular beacon • PPD,CBC with differential, CMP, HIV, HBsAg, anti-HCV, visual acuity/color vision

  8. NAA Liquid media AFB Solid media Douglas Moore, unpublished

  9. Mycobacteriology Flow Specimen AFB smear/stain PCR/MTD Broth and plate cultivation rRNA hybridization M. tuberculosis complex M. avium complex M. gordonae Other MOTT Broth sensitivities for SIRE & Z Plate confirmation/proportional method SIREZ and key second line drugs

  10. Questions • Any further testing needed? • Should she be hospitalized? • Should treatment be started? • With what? • What else do you need to do?

  11. Criteria for Hospitalizing TB Patients • Severe illness (e.g., resp distress, altered mental status, unstable vital signs, inanition, etc.) • Nowhere to go • Homeless/quasi homeless • Vulnerable population at home • Congregate setting (e.g., LTCF, jail)

  12. Questions • Any further testing needed? • Should he be hospitalized? • Should treatment be started? • With what? • What else do you need to do?

  13. Spontaneous mutations develop as bacilli proliferate to >108

  14. INH RIF PZA Multidrug therapy: No bacteria resistant to all 3 drugs Drug-resistant mutants in large bacterial population Monotherapy: INH-resistant bacteria proliferate INH

  15. Spontaneous mutations develop as bacilli proliferate to >108 INH resistant bacteria multiply to large numbers INH RIF INH INH mono-resist. mutants killed, RIF-resist. mutants proliferate  MDR TB

  16. Drug Resistance:Contributing Factors • Monotherapy • Inadequate dosing • Malabsorption • Heavy bacillary load • Frequent treatment interruptions • Non-adherence • Intolerance-based interruptions

  17. S H R Z E

  18. MOST COMMON REGIMENS • Standard • 2 HRZ(E)5-7 + 4-7 HR2 • 0.5 HRZ(E)5-7 + 1.5 HRZ(E)2 + 4-7 HR2 • Alternative regimens • 6RZE • 9HR • 12RE(+/-MOXI) • 18HE • 2HZSE + 7HZS

  19. Questions • Any further testing needed? • Should he be hospitalized? • Should treatment be started? • With what? • What else do you need to do?

  20. Public Health Responsibilities • Notify the local TB control program by telephone within 24 hours of suspicion of TB. • PHSKC TB Control: (206) 744-4579 • Treatment and discharge plans must be approved by the TB Control Officer • TB Control usually needs 48 hours

  21. General Criteria for Hospital Discharge • Medically stable (and tolerating anti-TB therapy if started) • Other acute medical problems addressed • DOT, case management, and clinical follow-up arranged • Adequate housing and, if necessary, home care • Household contacts <5y/o or immunosupressed have been addressed

  22. Directly Observed Therapy Chaulk CP, et al. JAMA 1998;279:943 • Preferred for all cases when resources permit • King County DOT prioritization: • Pulmonary involvement • HIV+ • Homeless • EPTB with adherence problems

  23. Case 1--Follow-up • She was placed on 4 TB drugs (INH, RIF, EMB, PZA). • Discharged back to place of residence • No high risk contacts • 4 wks into therapy, symptoms unchanged • Still 4+ AFB in sputum

  24. ONE MONTH INTO THERAPY

  25. Case 1--Sensitivity Results • Broth sensitivities return: IRES resistant; PZA and plates with first and second-line drugs pending • What now?

  26. Keys to MDR Management • Use any first line drugs available • Injectable • Fluoroquinolone • If not on ≥4-5 effective drugs, add one or more of the following: • Ethionamide • Cycloserine • Para-aminosalicylate • Repeat sensitivities • Continue injectable for 6 months and oral drugs for 18-24 months post-sputum culture conversion. • Consider referral for surgical excision

  27. Case 1--Expanded Regimen • Started capreomycin, moxifloxacin, cycloserine and PAS • Severe nausea and anorexia with normal LFTs--switched PAS to ethionamide • Depression/anxiety--SSRI started • Hypothyroid--T4 started • Final susceptibilities • 100% res: INH, RIF, PZA, Strep, amikacin • Partial resistance: EMB, PAS, capreomycin • 0% res: ofloxacin, ethionamide, cycloserine

  28. 1 MONTH AFTER REGIMEN CHANGE

  29. 2 MONTHS AFTER REGIMEN CHANGE

  30. Case 1 • Cultures converted 2 months after expanded regimen started • Capreomycin discontinued 6 months later • MOXI, CS, ETA, EMB discontinued p 24mos • Residual RUL fibrosis • Now under surveillance x24 months

  31. 6 MONTHS AFTER CULTURE CONVERSION

  32. 15 MONTHS AFTER CULTURE CONVERSION

  33. END OF THERAPY

  34. Local Epidemiology of TB

  35. Tuberculosis Epidemiologic Profile, 2006; WA DOH

  36. Tuberculosis Epidemiologic Profile, 2006; WA DOH

  37. Tuberculosis Cases Washington State 2006 Tuberculosis Epidemiologic Profile, 2006; WA DOH

  38. Tuberculosis Case RatesKing County 2001-07 PHSKC TB Control Program

  39. * *King County

  40. King County

  41. Homeless TB in King County by Treatment Start Date No. Cases 2002 2003 2004 2005 2006 2007 Treatment Start Date

  42. Horsburgh, NEJM 2004

  43. Case 2 • 43 y/o US born, homeless male • Fever, chest pain, neck swelling, nausea, and anorexia for about 3 weeks • HIV positive since 1998 • Not on ARV therapy

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