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TUBERCULOSIS Diagnosis & treatment Dr. Fazli Wahab FCPS(Med), FCPS(Pulmonology) Assisstant Prof Peshawar Medical College Diagnostic Tools Microscopy ◦ AFB smear ◦ Histology AFB Culture Radiology Tuberculin skin test Serological Tests AFB smear Rapid and inexpensive Granuloma Mycobacterial Culture Definitive diagnosis Growth detected after 4–8 weeks. Radiographic Procedures The "classic" picture is that of upper-lobe disease with infiltrates and cavities, X-ray chest appearance can be any of the following Infiltration Cavitations Fibrosis with traction Enlargement of hilar and mediastinal lymph node Pleural effusion/empyema Nodular/ Miliary shadows Mantoux Tuberculin Test (MT)/ Tuberculin Skin Test (TST) Test TB infection in adults and children Patient status Healthy individuals with no exposure history Positive Result >15mm Healthy individuals with exposure history or risk factors >10mm HIV +ve >5mm Serological Tests Not routinely used Polymerase Chain Reaction (PCR) Interferon Gamma release assays (IGRS) Enzyme Assays & Chromatographic assays: ◦ ◦ ◦ ◦ Unreliable & Ineffective methods No role in diagnosis in any form of TB Mycodot assay ICT TB Treatment Two aims ◦ Interrupt transmission ◦ Prevent morbidity and death. Anti-tuberculosis Drugs 1ST LINE DRUGS: • Isoniazid (H) • Rifampicin (R) • Pyrazinamide (Z) • Ethambutol (E) • Streptomycin (S) 1st line ATT Mode of Action Daily Dose (mg/kg) Isoniazid (H) Bactericidal 5 (4-6) Rifampicin (R) Bactericidal 10 (8-12) Pyrazinamide (Z) Bactericidal 25 (20-30) Streptomycin (S) Bactericidal 15 (12-18) Ethambutol (E) Bacteriostatic 15 (15-20) Regimens Standard short course regimens 6-8 months. An initial, intensive or bactericidal, phase and A continuation, or sterilizing, phase. DOTS DOTS (directly observed treatment, short-course), the WHO-recommended TB control strategy. New Cases •Sputum smear positive pulmonary TB •Sputum smear negative pulmonary TB •Extra-pulmonary tuberculosis WHO Category I: •New SS +VE Pulmonary TB •Severe Extra-Pulmonary •Severe SS –VE Pulmonary TB WHO Category III: New SS-VE Pulmonary TB Extra-Pulmonary (less severe) Initial Intensive Phase HRZE : 2 Months Continuation Phase HR: 4months OR HE: 6 Months RE-TREATMENT CASES/ WHOCategory II: •Relapse •Treatment Failures •Smear positive patients who have taken ATT for more than one month and defaulted INITIAL INTENSIVE PHASE (3months) HRZES: 2MONTHS Then HRZE:1 Month CONTINUATION PHASE HRE: 5 Months No Treatment is better than Poor Treatment Drug-resistant TB is caused by: ◦ Inconsistent or partial treatment, when patients do not take all their medicines regularly for the required period. ◦ Doctors and health workers prescribe the wrong treatment regimens, or because ◦ The drug supply is unreliable. The ultimate result is the multidrug-resistant TB (MDR-TB) or extensively-drug resistant TB (XDR-TB) In MDR-TB the Mycobacterium Tuberculosis is resistant to Rifampacin and INH with or without resistance to other 1st ATT. Treatment is difficult and expensive. Prevention The best way to prevent tuberculosis is to Treat. Additional strategies include ◦ BCG vaccination and ◦ Treatment of persons with latent tuberculosis infection who are at high risk of developing active disease. ATT in Special situations Pregnancy Infants of T.B. mothers & Breast Feeding Women on O.C.P Renal Impairment ATT Induced Hepatitis HIV - Infected or AIDS Pregnancy H, R, Z, E : Safe Streptomycin: Ototoxic May cause deafness in babies Contraindicated 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 Infants of T.B. mothers & Breast Feeding 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 Renal Impairment General principle: ◦ Standard chemotherapy ◦ Standard duration ◦ Dose interval modification Rifampicin and INH ◦ Safe and use normal dose Pyrazinamide ◦ Needs dose interval adjustment Renal Impairment Ethambutol ◦ Nephrotoxic , Renal excretion - 80% unchanged ◦ Ocular toxicity – dose dependent ◦ Serum monitoring required Amino glycosides – Streptomycin ◦ Nephrotoxic, renal excretion- 80% unchanged ◦ Needs dose interval adjustment in all stages New recomandations ◦ Avoid Aminoglycosides ATT Induced Hepatitis Usually present early but may present any time Mild / transient derangement in LFTs is normal (15 – 20 %) TYPES: ◦ Hepatocellular: ◦ Cholestatic ◦ Mixed 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 Management ↑ 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 Management ↑ ALT/AST (>Thrice normal) + Symptoms ◦ Anorexia, Nausea, Vomiting, Abdominal Pain , Jaundice ◦ STOP ATT ↑ ALT/AST (>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 Management 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 Thanks