Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo TUBERCULOSIS SAPRAA 23rd March 2007 Dr Joe Khoali Medical Advisor Gauteng TB Control Programme TB CAN BE CURED! TB anywhere is TB everywhere! Definition of terms Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo TB CAN BE CURED! TB anywhere is TB everywhere! • Mycobacterium species/Mycobacteria/Acid fast bacilli – family of bacteria to which bacterium causing TB belongs – this big family includes other bacteria similar in structure to TB bacteria but do not cause tuberculosis disease • Mycobacterium tuberculosis (MTB)/TB bacillus – the mycobacterium that specifically causes tuberculosis disease • Pulmonary tuberculosis – tuberculosis of the lungs • Extra-pulmonary tuberculosis – tuberculosis disease outside of the lung e.g. bone, brain, blood etc Def. cont. Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo TB CAN BE CURED! TB anywhere is TB everywhere! • Smear microscopy – examination of patient specimen under the microscope • Culture – cultivation of mycobacteria in the laboratory using special media • Drug susceptibility testing (DST) – test for ability of anti-TB drugs to kill TB bacilli • MDRTB – multiple drug resistant TB (isoniazid & rifampicin), • XDR – extensive drug resistant TB – (MDR + fluoroquinolone+(kanamycin or amikacin or capreomycin) GAUTENG TB PROGRESS REPORT Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo TB CAN BE CURED! TB anywhere is TB everywhere! 2004 2005 2006 Incidence per 100 000 373 per 100 000 376 per 100 000 444 per 100 000 Pulmonary TB 30 792 34 017 32 459 All TB cases 40 163 44 152 43 377 New Smear Positive cases 23 806 21 531 18972 Bacteriological coverage 93.3% 94.4% 89.9% New smear Positive Conversion Rate 75% 64.9% New Smear Positive Cure Rate 13 521 (62.4) 15 758 (66.7%) Treatment Interruption Rate 1769 (8.2%) 6.9% Treatment success rate 67.7% 71.4% Deaths 1983 (9%) 2283 (9.5%) Failure Rate 267 (1.2%) 371 (1.6%) MDR TB 118 (0.2%) 129 (0.26%) Background Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo TB CAN BE CURED! TB anywhere is TB everywhere! 4 combination drugs introduced in 2000 Reasons for introduction: fewer drugs prevention of resistance better ordering system one expiry date easier administration (DOT) Back. cont. Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo TB CAN BE CURED! TB anywhere is TB everywhere! Establishment of WHO-GDF since 2001 Rationale Reduction of TB drug costs Donor funding for purchase of TB drugs Standardised regimen world wide Prevention of MDR-TB SA started using 4FDC before this process Advantages of FDCs Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo TB CAN BE CURED! TB anywhere is TB everywhere! • • • • • Fewer drugs improve compliance Correct therapeutic levels Fewer side effects – only 3 – 6% so far Calculation of needs simpler Drug ordering, stock control and storage is easier Reduced Tablets Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo TB CAN BE CURED! TB anywhere is TB everywhere! Body weight Single drugs FDCs <35kg 7 – 12 2 <40kg 8 – 14 3 <50kg 9 – 17 3 <60kg 12 – 21 4 <70kg 13 – 25 5 Justification for dosage formulations Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo TB CAN BE CURED! TB anywhere is TB everywhere! • Different populations of TB bacilli - metabolically active - intermediately active - semi-dormant bacilli (persisters) - dormant bacilli Action of TB drugs Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo Drug Rif X X X INH X X X PZA X X Eth TB CAN BE CURED! TB anywhere is TB everywhere! Bacteriostatic Bacteriocidal Intracellular Extracellular Strep X X Regimen 1 Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo Pre treament body weight Initial phase 2 months 5 x a week Continuation phase 4 months 5 times a week TB CAN BE CURED! TB anywhere is TB everywhere! 3 times a week RHZE 150/75/400/ 275 RH 150/75 RH 300/150 RH 150/150 RH 300/150 30-37 kg 2 tablets 2 tablets 2 tablets 38-54 kg 3 tablets 3 tablets 3 tablets 55-70 kg 4 tablets 2 tablets 3 tablets 71kg 5 tablets 2 tablets 3 tablets Regimen 2 Pretreatm ent body weight Initial phase 2 months 5 times a week Initial phase month 3 5 times a week Continuation Phase 5 times a week RHZE 150/75/400/ 275 Streptomycin (g) RHZE 150/75/400 /275 RH 150/75 E 400 30-37 kg 2 tabs 0.5 2tabs 2 tabs 2 tabs 38-54 kg 3 tabs 0.75 3 tabs 3 tabs 2 tabs 55-70 kg 4 tabs 1.0 71 kg 5 tabs 1.0 Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo TB CAN BE CURED! TB anywhere is TB everywhere! RH 300/150 E 400 4 tabs 2 tabs 3 tabs 5 tabs 2 tabs 3 tabs Fixed Dose Combination tablets for children. Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo TB CAN BE CURED! TB anywhere is TB everywhere! • RHZ: 60/30/150 • RH: 60/30 • RH: 60/60 (for three times weekly regimen) Chemoprophylaxis. Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo TB CAN BE CURED! TB anywhere is TB everywhere! • All children contacts less than 5 years of infectious (smear positive) cases should be examined. – Healthy prophylaxis - INH 5mg/kg daily for 6 months – If TB treat - RHZ Treatment of TB /HIV Co-infection Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo • Guideline is clear on how to manage concomitant TB/HIV disease – TB being the commonest OI • Principle is to screen for TB on entrance to programme • 2 scenarios TB CAN BE CURED! TB anywhere is TB everywhere! – Develop TB while on ART’s – TB before commencing ART Approved ARVL RX Regimens 1a. Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo 2 NRTI’s + NNRTI e.g. d4T+3TC+ Efavirenz i.e. Stavudine+Lamivudine+ Stocrine 1b. 2 NRTI’s + NNRTI e.g. d4T+3TC+ Nevirapine i.e. Stavudine+Lamivudine+ Viramune 2. 2NRTI’s + PI e.g. AZT+ddi+ Kalitra i.e. Zidovudine+ Didanosine+Lopinavir/Ritanovir TB CAN BE CURED! TB anywhere is TB everywhere! TB and ART’s Interactions Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo • Rifampicin is a powerful inducer of Cytochrome P450 enzymes • Avoid the use of PI’s with TB drugs • Substitute PI’s with NNRTI’s e.g. EFV or NVP • AZT and DDI may interfere with absorption of Rifampicin TB CAN BE CURED! TB anywhere is TB everywhere! (I.e. Treat TB first and HIV thereafter) Treatment cont. • Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo TB before commencing ART – No history of stage IV and CD4>200 = no ART. Assess after completion of TB treatment – If history of stage IV disease and/or CD4<200, complete 2 months of TB treatment before commencing ART – If CD4<50 and patient tolerating TB treatment, initiate ART after 2/52 of TB treatment. Avoid nevirapine. TB CAN BE CURED! TB anywhere is TB everywhere! Treatment cont. Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo TB CAN BE CURED! TB anywhere is TB everywhere! • Develop TB on ART – Regimen 1a = continue – Regimen 1b = change NVP to Efivarenz – Regimen 2 = increase the dose of the kaletra combination until two weeks after completion of TB treatment, then restart the normal doses. Common Adverse Reactions Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo Caused by Adverse reaction Signs and symptoms Isoniazid Peripheral neuropathy Tingling sensation in hands and feet Itchy skin, rash Allergy Pyrazinami Gastrointestinal intolerance de Athralgia Arthritis TB CAN BE CURED! TB anywhere is TB everywhere! Upset stomach, vomiting Joint aches Gout (rare) Common Adverse Reactions Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo Caused by Adverse Reaction Signs and Symptoms Ethambutol Eye damage Blurred or changed vision Altered color vision Streptomycin Ear damage Balance problems Hearing loss Ringing in the ears Itchy skin Allergy TB CAN BE CURED! TB anywhere is TB everywhere! Common Adverse Reactions Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo TB CAN BE CURED! TB anywhere is TB everywhere! Caused by Adverse reaction Signs and symptoms Rifampicin Gastrointestinal intolerance Anorexia, nausea, abdominal pain Isoniazid, PZA, Rifampicin Hepatitis Abdominal pain, anorexia, nausea, vomiting, abnormal LFTs Management of Adverse Reactions Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo TB CAN BE CURED! TB anywhere is TB everywhere! • Gastrointestinal intolerance • • • Skin reactions • Take treatment at bedtime Refer if severe intolerance eg nausea, vomiting Reassure, topical/oral anti-histamines • Hepatitis • Establish alcohol intake • All other adverse/severe reactions • Refer Drug Interactions Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo TB CAN BE CURED! TB anywhere is TB everywhere! • Relatively few drug interactions substantially change concentrations of TB drugs • TB drugs sometimes change concentrations of other drugs • Isoniazid increases phenytoin concentration to toxic levels • Rifampicin may reduce effect of oral diabetic drugs, contraceptives, digoxin, oral anticoagulants, phenobarbitones. • Always refer patients for dosage adjustments Multi-drug resistant TB Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo • • • • • TB CAN BE CURED! TB anywhere is TB everywhere! Increase in MDR-TB cases is an indication of a poor performing TBCP. MDR-TB is a man-made disease. Laboratory diagnosis Primary resistance (no history of TB Rx) Acquired resistance (previous hx of TB Rx) Risk factors for development of MDR-TB Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo TB CAN BE CURED! TB anywhere is TB everywhere! • • • • • • • Previously unsuccessful TB treatment. Interruption of TB treatment Inappropriate TB treatment regimen. Inappropriate TB treatment duration Previous TB treatment in a hospital High TB prevalence. HIV+ is not an independent risk factor MDR-TB PREVALENCE in South Africa (2002) Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo • New cases: 1.7% (range 1 – 2.4%) • Re-treatment cases: 6.6% (range 1.6–13.9%) XDR-TB prevalence not known TB CAN BE CURED! TB anywhere is TB everywhere! MDR-TB treatment concerns Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo TB CAN BE CURED! TB anywhere is TB everywhere! • Difficult and expensive to treat. [R28,000 vs R400 patient] • Intensive phase of 4 months, continuation phase 12 months or more • Second-line TB drugs cause more side effects. • Less effective: Only 50% cure rate. • Some cases never convert to negative. Second-line TB drugs Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo • Classes Category (6) Drug(s) 1 Aminoglycosides Kanamycin Amikacin Capreomycin Polypeptides 2 Thioamides Ethionamide Prothionamide 3 Pyrazinamide Pyrazinamide 4 Fluoroquinolones Ofloxacin Ciprofloxacin 5 Cycloserine / Terizidone Cycloserine / Terizidone 6 Ethambutol Ethambutol 7 PAS PAS TB CAN BE CURED! TB anywhere is TB everywhere! Classification of drugs available for treatment of MDR-TB Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo • Activity Moderate bactericidal Low bactericidal Bacteriostatic TB CAN BE CURED! TB anywhere is TB everywhere! Drug/Category Aminoglycosides Thioamides Pyrazinamide (acid pH) Fluoroquinolones Ethambutol Cycloserine / Terizidone PAS Designing MDR-TB Treatment Regimens Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo TB CAN BE CURED! TB anywhere is TB everywhere! • Minimum of four drugs necessary during intensive phase (usually five drug combination) • At least three drugs not administered previously for more than three months • One drug option per category due to crossresistance • Drugs selected from highest ranking categories • Aminoglycoside/Polypeptides must be included during the intensive phase • Fluoroquinolone must be included throughout General Treatment Principles Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo • Provide 18-24 months’ treatment, always with intensive phase of at least 4 months • PROVIDE DOT THROUGHOUT • Warn patients about side-effects • Manage side-effects appropriately • Perform cultures monthly TB CAN BE CURED! TB anywhere is TB everywhere! Treatment Approaches Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo • Standardised – All patients on the same regimen, irrespective of drug susceptibility results – NTCP policy in South Africa since 2000 • Individualised – Regimen tailor-made according to drug susceptibility pattern of strain TB CAN BE CURED! TB anywhere is TB everywhere! Standardised Regimen Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo • According to ethambutol resistance – Intensive phase (4 months) • kanamycin, ofloxacin, ethionamide, pyrazinamide, ethambutol or terizidone TB CAN BE CURED! TB anywhere is TB everywhere! – Continuation phase (12 – 18 months)* • ofloxacin, ethionamide, ethambutol or terizidone * (Shortened to 12 months following culture conversion) – Dose standardised according to three weight bands (<50kg, 50-65kg, >65kg) Treatment Monitoring Department of Health Lefapha la Maphelo Department van Gesondheid Umnyango wezeMpilo TB CAN BE CURED! TB anywhere is TB everywhere! • Our fundamental responsibility • Ensure adherence – DOT with patient centered case management i.e education, reassurance • Sputum collection by end of 8 weeks to assess response - SCR • Check susceptibility if still positive at three months • Periodic evaluation (minimum monthly) to assess adherence and identify adverse reactions