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Review evaluation basics, lab services, local epidemiology, and PHSKC cooperation. Includes case studies and diagnostic examinations. Learn about drug resistance, common regimens, and public health responsibilities. Follow-up with case studies and MDR management. |
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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 • Case studies touching on common problems in TB management
Case 1 • 24 y/o Tibetan arrived 12 months ago • Cough, sputum, fever, night sweats, weight loss • No prior TB treatment history
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
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
Questions • Any further testing needed? • Should he be hospitalized? • Should treatment be started? • With what? • What else do you need to do?
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
NAA Liquid media AFB Solid media Douglas Moore, unpublished
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
Questions • Any further testing needed? • Should she be hospitalized? • Should treatment be started? • With what? • What else do you need to do?
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)
Questions • Any further testing needed? • Should he be hospitalized? • Should treatment be started? • With what? • What else do you need to do?
Spontaneous mutations develop as bacilli proliferate to >108
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
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
Drug Resistance:Contributing Factors • Monotherapy • Inadequate dosing • Malabsorption • Heavy bacillary load • Frequent treatment interruptions • Non-adherence • Intolerance-based interruptions
S H R Z E
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
Questions • Any further testing needed? • Should he be hospitalized? • Should treatment be started? • With what? • What else do you need to do?
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
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
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
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
Case 1--Sensitivity Results • Broth sensitivities return: IRES resistant; PZA and plates with first and second-line drugs pending • What now?
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
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
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
Tuberculosis Cases Washington State 2006 Tuberculosis Epidemiologic Profile, 2006; WA DOH
Tuberculosis Case RatesKing County 2001-07 PHSKC TB Control Program
* *King County
Homeless TB in King County by Treatment Start Date No. Cases 2002 2003 2004 2005 2006 2007 Treatment Start Date
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