TBRx - CURRENT CONCEPTS IN MANAGEMENT OF TUBERCULOSIS...

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CURRENT CONCEPTS IN MANAGEMENT OF TUBERCULOSIS
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Pre Streptomycin era: – Rest - Sanatorium/Affected portion of lung - Collapse therapy – Use of Gold Salts/Sulphones/Vit D 50% Mortality - PTB EVOLUTION OF DRUG THERAPY
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SM: MRC Trial, 1946 104 Patients SM Bed Rest Death 4 14 Culture 3mths 10 1 Neg 6 mths 8 2 Xray improve 69% 33% Inference: Immediate adv. in S arm 5 yr. FU: Most patients developed resistance BMJ 1948; 2: 769-82
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Duly Effective means of t/t TB. - 1950s: Primacy of chemotherapy over other forms established. • TRC, Chennai; 1959 (land mark study) 163 Patients Sanatorium Home (81) (82) At 1 year - Cure Rate 92% 90% Relapse Rate 10% 7% - Family contacts no more 11.5% 10.5% liable to contract TB Bull WHO. 1959 21:51-58 Domiciliary Treatment
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Cornerstone of effective t/t, prevents drug resistance. Initial studies: S alone for active PTB t/t failures/Relapse rates/R to S Tempel et al Pts 12g PAS Str. alone 1g-2g daily alone Drug Resistance 33% 73% PAS + Str. Combined No Resistance. Am Rev. Tuberc 1951; 63: 295-311 Multi Drug Theory
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Isoniazid & Effective Std t/t: • 1952: INH introduced as ATT • 1955: MRC– First national DR Survey with primary resistance Resistant to one strain T/T with 3 drugs phase lasting 2-3 mths 2 drug phase explored. T/T given for 12 mths : Failure Rate high because of failure to complete t/t
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1960s MRC Trial P + H + S – 6 wks P + H – 1 year P + H – 1 year t/t failure 3% 16% Tubercle 1962; 43: 201-219 Two Phase Chemotherapy
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Mid 1970s East African/MRC Trial (land mark study) Pts: 540 6SHR 6SHZ 6SHT 6SH 2SHT 16 HT Relapse 11% 22% 29% 4% 2% Short Course Therapy Culture Neg 69% at 2 mo 31% 25% 8%
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Inference: - R containing regimen- Effective - Relapses occurred within 1 year after ATT. - Min- toxicity ass. With multidrug regimens. (2.5% : Drugs Stopped) - Almost all relapse cases were with organisms (S) to S/H. Lancet 1972; 1: 1079-85
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East African/MRC Trial 700 Patients 6SHR 6 HR 2SHRZ/4HT 2 SHRZ /4 S 2 H 2 R 2 2% 5% 6% 4% Inference: ~ 100% Care Rate < 6% Relapse Rates, Susceptible organisms Intermittent therapy: Good Response Acceptant Relapse Rates. Am Rev Respir Dis 1977; 116: 3-8 Relapse
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Hong Kong Chest Service/MRC Trial 6 HZS 6 S 2 H 2 Z 2 6S 3 H 3 Z 3 Relapse 18-24% Therapy 9 mths. Relapse 5-6% Am Rev Respir Dis 1977; 115: 727-33.
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East African/MRC Trial (Shortest Course CT) 1980s 430 Patients 2 SHRZ 2 HRZ 2 SHRZ 2 HR 2 SHRZ 2 HZ 2 SHRZ/2H 2 HRZ/2H Relapse 16% 11% 32% 30% 40% Inference: Relapse Rates with 4 mths course Rifampicin essential Am Rev Respir Dis 1981; 123: 165-70
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TRC, Chennai; NTI, Bangalore 3 SHRZ 3 SHRZ/2 H 2 R 2 Z 2 3 SHZ/2 H 2 Z 2 Culture Conversion at 2 mths > 90% 74% Inference: - 3 mth. therapy not effective for smear +ve PTB.
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TBRx - CURRENT CONCEPTS IN MANAGEMENT OF TUBERCULOSIS...

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