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T.B. Special Situations

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    T.B. Special Situations T.B. Special Situations Presentation Transcript

    • Management of TuberculosisIn Special Situations
      Prof. Dr. Zafar Hussain Iqbal
      MBBS, DTCD, MRCP, FRCP
      Prof. of Pulmonology
      AIMC / JHL
    • Tuberculosis - Global
      TB is shadow of poverty
      1/3rd of the world population infected (1.7 billion)
      10% gets the disease
      10 million new cases each year
      4 million deaths each year
      Crash of Boeing 747 each hour every day
      1 untreated pt. infects 10-15 persons per year
      WHO declared TB as global emergency 1993
    • Tuberculosis - Pakistan
      Ranks 8th amongst 22 high burden countries
      Incidence 181 /100,000
      Est. no of new TB cases 297,108
      New sputum smear +ve81 /100,000
      Prevalence 329 /100,000
      Mortality 40 /100,000
      New MDR Tb cases 3.2 %
      (WHO Global TB Report Published in 2009 – Data of 2007)
    • Tuberculosis - Diagnosis
      Pulmonary TB
      Direct sputum smear microscopy - Gold Standard
      CXR – unreliable, helpful in smear negative cases
      Tuberculin testing – limited value in clinical work
      ESR – no diagnostic value
      Serological tests
      PCR
      Extra-Pulmonary TB
      Tissue smear for AFB and AFB culture
      Histology
      Clinical setting
    • Tuberculosis – Treatment
      New case
      Smear positive pulmonary TB
      Smear negative pulmonary TB
      Extra-pulmonary TB
      Initial intensive phase – 2 RHEZ
      Continuation phase – 6 RH or 6 HE
      Re-treatment
      Relapses
      Treatment failure
      Defaulter
      Initial phase – 2 RHEZ + S, 1 RHEZ
      Continuation phase – 5 RHE
    • Pregnancy
      • H, R, PZA, E : Safe, No evidence of teratogenecity or congenital malformations
      • Add Pyridoxine with INH to avoid small risk of CNS damage in infants
      • Rifampicin : High dose teratogenic in animals
      • Streptomycin: Ototoxic, may cause deafness in babies, Contraindicated
      • Capreomycin, Kenamycin, Viomycin
      • Ethionamide & Prothionamide: Teratogenic
    • Infants of T.B. mothers & Breast Feeding
      • Mothers must continue A.T.T during feeding
      • Child should not be separated
      • Mother should cover her mouth during cough particularly if smear +ve
      • INH prophylaxis : 5 mg/Kg 2 months
      • Do T.T - if –ve, stop INH, give BCG
      - if +ve, continue INH 4 months, then BCG
      • Do not give BCG while on INH
      • INH resistant BCG
      • Rifampicin + INH – 3 months
    • Women on O.C.P
      Rifampicin: Hepatic enzyme inducer
      O.C.P may become ineffective
      Rifampicin babies
      Extra / alternative protection required
      Higher dosage
    • Renal Impairment - CKD
      Acquired Immunodeficiency state - High risk of T.B.
      50% Tuberculin -ve
      Common in Asian and African origin in UK
      Three categories
      CKD
      Dialysis
      Transplant
      General principle - Standard chemotherapy, standard duration,
      Dose interval modification
      Creatinine clearance is a better indicator than serum creatinine
    • Grades Of Renal Impairment In CKD
      Stage 1 CKD : Normal CC with structural abnormality
      Stage 2 CKD : CC 60 – 90ml/ min
      Stage 3 CKD : CC 30 – 60ml/min
      Stage 4 CKD : CC 15 – 30ml/min
      Stage 5 CKD : CC < 15ml/min with or without dialysis
    • Renal Impairment
      Rifampicin:
      Safe , Active metabolite excreted in bile.
      Inactive metabolite (10%) excreted in urine
      Use normal dose in all stages
      INH
      Safe, Metabolized in liver .
      Add pyridoxine to avoid P.N.
      Use normal dose in all stages
    • Renal Impairment
      Pyrazinamide
      Metabolized in liver
      Delayed elimination of drug & metabolites in CKD 4 & 5
      Needs dose interval adjustment
      CKD 1-3 < 50kg : 1.5g daily
      > 50Kg : 2 g daily
      CKD 4-5 25-30 mg/Kg 3 x / week
    • Renal Impairment
      Ethambutol
      Nephrotoxic , Renal excretion - 80% unchanged
      Ocular toxicity – dose dependent
      Serum monitoring required – should be <1.0ug/ml
      CKD 1-3 15mg/kg daily
      CKD 4-5 15-25mg/Kg 3 x week
      Max 2.5 g
    • Renal Impairment
      Amino glycosides – Streptomycin
      • Nephrotoxic, renal excretion- 80% unchanged
      • Reduced clearance in elderly
      • Needs dose interval adjustment in all stages
      • 12-15mg/Kg - 2 or 3 time/week
      • Monitor serum levels, ensure trough levels (at 24hrs) of < 2 ugm/ml
      • New recomandations - avoid Aminoglycosides
      • Use Moxiflocacin - 400mg daily CKD 1-3
    • Renal Impairment
      Prothionamide : Safe, Billiary excretion
      Thiacetazone, PAS, Cycloserine
      Should be avoided
      Partially excreted by kidneys
    • Dose chart of ATT in CKDBTS Guidelines 2010
    • Chemoprophylaxis in CKD
      INH 6 months
      RH 3 months
      R 4-6months
      RZ 2 months
      Protective efficiency 60 -65 % with 6H
      50 % with 3 RH
      Long term use of INH not recommended
    • ATT in Hemodialysis
      Immediately after HD – To avoid premature removal
      4- 6 hrs before HD – To reduce toxicity
      R & H – Standard daily dose
      PZA – Standard dose – 3 x weekly
      Ethambutol - Standard dose – 3 x weekly
      Avoid Streptomycin
    • ATT in Renal Transplant
      Standard dosage and duration of HRZE
      May need modification until normal renal function
      Ethambutol can be replaced with Moxifloxacin
      RifampicinHepatic enzyme inducer – risk of graft rejection
      Dose adjustment for Ciclosoprin,TacrolimusMycofenolate
      Double the dose of steroids
    • ATT Induced Hepatitis
      • Usually present early but may present any time
      • More with fixed drug combination than with split regimen
      • Mild / transient derangement in LFTs is normal (15 – 20 %)
      • TYPES – Hepatocellular , Cholestatic , Mixed
      • Check viral serology (B,C) in all patients who develop hepatitis while on ATT
    • ATT Induced Hepatitis
      RISK FACTOR
      • Age >35 years
      • Female sex
      • Oriental race (EAST ASIAN)
      • Pre-existing liver disease
      • Extensive tuberculosis
      • High alcohol consumption
      • Malnutrition and hypo Albuminemia
      • Other hepatotoxic drugs
      • Slow Acetylator status
      • High dosage in relation to body weight
    • ManagementRecommendation Of Joint TB Committee Of BTS
      • ↑ ALT/AST (< Twice normal)
      - Continue ATT
      - Check after 2 weeks
      • ↑ ALT/AST (>Twice normal)
      - Continue ATT
      - Check LFTs weekly for 2 weeks
      - Then every 2 weeks until normal
      • ↑ ALT/AST (>Thrice normal) + Symptoms
      - Anorexia, Nausea, Vomiting, Abdominal Pain , Jaundice
      - STOP ATT
    • Recommendation Of Joint TB Committee Of BTS
      AST/ALT (>5 time normal) OR ↑ Bilirubin
      Even If Patient Asymptomatic
      Stop ATT
      If patient is smear –ve / Clinically stable
      - Wait until LFTs are normal
      - No need for alternate drugs
      If patient is smear +ve / Clinically unstable
      - Start Ethambutol, Streptomycin and one of the reserve drugs until LFT‘s are normal
      - Continue safe drugs until LFTs are normal
    • Recommendation Of Joint TB Committee
      When LFT’s are normal
      • Reintroduce ATT to detect offending drugs
      • Start with least hepatotoxic one by one
      INH > RIF > PZA
      If no reaction
      • Continue ATT
      • Stop alternate drugs
      If reaction has developed
      • Stop offending drug
      • Continue remaining drugs
      • Ensure adequate regimen and duration
    • HIV - Infected or AIDS
      Standard regimen – usually good response
      Drug reactions more common
      Thiacetazone should be avoided
      Prolonged treatment
      Patients on Anti-retroviral therapy- high risk of interaction with Rifampicin
      withhold ATT during this period
    • SILICOSIS
      More prone to develop P.T.B
      Difficult to treat - Impaired macrophages function Poor penetration of drug in P.M.F
      Hong Kong study – rock islands of Granite 40% suffer from P.T.B
      High relapse rate – 22 to 33% : 2 & 5 years
      Slower sputum conversion
      Standard regimen, longer duration
    • THANK YOU