Thank you for viewing this presentation. We would like to remind you that this material is the property of the author. It is provided to you by the ERS for your personal use only, as submitted by the author. 2012 by the author Evidence provided by recent metanalyses on treatment: what is new? GB Migliori WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Tradate Italy Aims • • • • • To describe and discuss: Existing guidelines and definitions Epidemiology of MDR-TB in Europe and globally derived from surveillance and M&E (Monitoring and Evaluation) The new information on MDR-TB diagnosis The new information on MDR-TB treatment deriving from recent meta-analyses The principles of MDR-TB control, with prevention and public health aspects 3 Aims • • • • • To describe and discuss: Existing guidelines and definitions Epidemiology of MDR-TB in Europe and globally derived from surveillance and M&E (Monitoring and Evaluation) The new information on MDR-TB diagnosis The new information on MDR-TB treatment deriving from recent meta-analyses The principles of MDR-TB control, with prevention and public health aspects 4 200 0 5 6 Guidelines for the programmatic management of drug-resistant tuberculosis (1) 1 Background information on DR-TB 2 Framework for effective control of DR-TB 3 Political commitment and coordination 4 Definitions: case registration, bacteriology and treatment outcomes 5 Case-finding strategies 6 Laboratory aspects 7 Treatment strategies for MDR-TB and XDR-TB 8 Mono- and poly-resistant strains 9 Treatment of DR-TB in special conditions and situations 10 DR-TB and HIV infection 11 Initial evaluation, monitoring of treatment and management of adverse effects 7 Guidelines for the programmatic management of drug-resistant tuberculosis (2) 12 Treatment delivery and community-based DR-TB support 13 Management of patients with MDR-TB treatment failure 14 Management of contacts of MDR-TB patients 15 Drug resistance and infection control 16 Human resources: training and staffing 17 Management of second-line antituberculosis drugs 18 Category IV recording and reporting system 19 Managing DR-TN through patient-centered care ANNEX 1 Drug information sheets ANNEX 2 Weight-based dosing of drugs for adults ANNEX 3 Suggestions for further reading ANNEX 4 Legislation, human rights, and patient’s right in TB care prevention and control ANNEX 5 Use of experimental drugs outside of clinical trials 8 ANNEX 5 Methodology Causes of DR 9 Causes of MDR Patient mismanagement 10 DOTS FUNDING: Government Commitment (10$/ case) DIAGNOSIS: SS microscopy, QA and safety measures MDR-TB > money Up to 20,000 $/ case +C, DST, SRL, QA, infection control TREATMENT: SCC,DOT, 6-8 months, no hospitalization 24 months, mandatory DOT & hospitalization in reference facilities TB drugs only, no AE relevant toxicity, need special drugs + expertise TREATMENT MONITORING: SS, standard outcome definitions C, DST, special outcome definitons 11 Definitions • • • • Mono-R Poly-R MDR XDR • SS+, C+ • Cure, failure • Treatment monitoring 12 Definitions MDR-TB = Strains resistant to at least INH and RIF (most important 1st-line drugs) XDR-TB = MDR TB strains with additional resistance to any fluoroquinolone and any of the 3 injectable second-line drugs (amikacin, kanamycin, capreomycin) TDR, XXDR = Resistance to all drugs (not standardised defin) TB with any MDR TB drug resistance TDR/XXDR TB XDR TB XDR= HR + 1 FQ + 1 Injectable (KM or AMK or CM) 1st-line oral •INH Injectables •RIF •SM Fluoroquinolones •PZA •KM •Cipro •EMB •AMK •Oflox •Levo •CM •(Rfb) •Moxi •(Gati) Oral bacteriostatic 2nd line •ETA/PTA •PASA •CYS Unclear efficacy Not routinely recommended, efficacy unknown, e.g., amoxacillin/clavulanic acid, clarithromycin, clofazamine, linezolid, inmipenem/cilastatin, 14 high dose isonizid Aims • • • • • To describe and discuss: Existing guidelines and definitions Epidemiology of MDR-TB in Europe and globally derived from surveillance and M&E (Monitoring and Evaluation) The new information on MDR-TB diagnosis The new information on MDR-TB treatment deriving from recent meta-analyses The principles of MDR-TB control, with prevention and public health aspects 15 Notified cases of MDR-TB Estimated absolute numbers of reported cases with MDR-TB* Notified cases of MDR-TB Cases of MDR-TB <100 0–99 100–999 100–999 1000–9999 1000–9999 ≥10 000 >10,000 NA *among reported pulmonary TB patients Distribution of MDR-TB among new TB cases, 1994-2010. 0-<3 3-<6 6-<12 12-<18 >18 No data available Subnational data only 17 Distribution of MDR-TB among previously treated TB cases, 1994-2010. 0-<6 6-<12 12-<30 30-<50 >50 No data available Subnational data only 18 13 top settings with highest % of MDR-TB among new cases, 2001-2010 35.3 Preliminary results ERJ 2012 Minsk, Belarus (2010) 28.3 Murmansk Oblast, Russian Federation (2008) 27.3 Pskov Oblast, Russian Federation (2008) 23.8 Arkhangelsk Oblast, Russian Federation (2008) 22.3 Baku city, Azerbaijan (2007) 20.0 Ivanovo Oblast, Russian Federation (2008) Republic of Moldova (2006) 19.4 Kaliningrad Oblast, Russian Federation (2008) 19.3 Belgorod Oblast, Russian Federation (2008) 19.2 Dushanbe city and Rudaki district, Tajikistan (2009) 16.5 Mary El Republic, Russian Federation (2008) 16.1 Donetsk Oblast, Ukraine (2006) 16.0 Estonia (2008) 15.4 Tashkent, Uzbekistan (2005) 14.8 0 5 10 15 20 25 30 Notifications of MDR-TB increasing BUT only ~ 1 in 6 (16%) of estimated cases of MDR-TB among reported TB patients diagnosed and treated in 2010 MDR-TB cases treated and estimated numbers not treated for MDR-TB, among notified TB patients, 2010 Notified cases of MDR-TB 60 290,000 300 50 53,000 Not on treatment 250 Treated 40 200 30 150 20 100 2010 or ld 2009 W 2008 Am R er ic as 2007 A 2006 W 2005 EM 0 ic a 0 Af r 50 si .P a ac ifi c Eu ro pe 19,000 10 SE Number of patients (thousands) Global Plan target ~270,000 in 2015 Proportion of TB patients tested for MDR-TB remains low New cases 40% Previously treated 60% 51% 35% 50% 30% % of patients Global plan target for 2015 = 20% 25% 20% 15% 40% Global plan target for 2015 = 100% 30% 20% 19% 10% 10% 2% 0.3% Af r ic a 0% Pa ci fic SE A si a W O R LD W O R LD ic a Af r R 0% EM 3% 2% R 0.4% 0.2% 0.1% EM 1% Eu ro p Am e er ic as 5% 6% 6% W 5% Eu ro p Am e er ic as SE A si a W Pa ci fic % of patients 30% Trend of MDR-TB among new cases, Estonia, Latvia and…Tomsk Oblast, RF 70 0.35 60 0.30 50 0.25 40 0.20 30 0.15 20 0.10 Estonia 10 0 1997 1999 2001 2003 2005 0.05 0.00 1997 2007 100 90 80 0.35 70 60 50 40 30 0.25 20 10 0 1997 p=0.6213 1999 2001 2003 2005 0.30 0.20 0.15 0.10 Latvia 1999 2001 2003 2005 2007 0.05 0.00 1997 120 0.35 100 0.30 p=0.3260 1999 2001 2003 2005 0.25 80 0.20 60 0.15 40 Tomsk oblast, RF 20 0 1998 2000 2002 2004 TB notification rate 2006 0.10 p=0.0055 0.05 0.00 1997 1999 2001 2003 % MDR among new 2005 22 Countries that had reported at least one XDR-TB case by Oct 2011 Argentina Armenia Australia Austria Azerbaijan Bangladesh Belarus Belgium Benin Botswana Brazil Burkina Faso Bhutan Cambodia Canada Chile China Colombia Czech Republic Dominican Republic Ecuador Egypt Estonia Japan France Kazakhstan Georgia Kenya Germany Kyrgyzstan Greece Latvia India Lesotho Indonesia Lithuania Iran (Islamic Rep. of) Mexico Ireland Mongolia Israel Mozambique Italy Myanmar Namibia Nepal Netherlands Niger Norway Pakistan Peru Philippines Poland Portugal Qatar Republic of Korea Republic of Moldova Romania Russian Federation Slovenia South Africa Spain Swaziland Sweden Tajikistan Thailand The Former Yugoslav Republic of Macedonia Togo Tunisia Turkey Ukraine United Arab Emirates United Kingdom United Republic of Tanzania United States of America Uzbekistan Viet Nam Aims • • • • • To describe and discuss: Existing guidelines and definitions Epidemiology of MDR-TB in Europe and globally derived from surveillance and M&E (Monitoring and Evaluation) The new information on MDR-TB diagnosis The new information on MDR-TB treatment deriving from recent meta-analyses The principles of MDR-TB control, with prevention and public health aspects 24 ulture and DST laboratories to diagnose MDR-TB, 2010 20/36 HBCs* have insufficient capacity to diagnose MDR-TB Culture and DST laboratories to diagnose MDR-TB, 2010 Laboratories per 5M population ≥1 ≥1 Culture and DST <1 <1 laboratories per 5M, 2010 *HBC= high-burden country NA Countries = Afghanistan, Armenia, Azerbaijan, Bangladesh, Belarus, Brazil, Bulgaria, Cambodia, China, DR Congo, Estonia, Ethiopia, Georgia, India, Indonesia, Kazakhstan, Kenya, Kyrgyzstan, Latvia, Lithuania, Mozambique, Myanmar, Nigeria, Pakistan, Philippines, Republic of Moldova, Russian Federation, South Africa, Tajikistan, Tanzania, Thailand, Uganda, Ukraine, Uzbekistan, Viet Nam, Zimbabwe The “magic” Gene Xpert The message Any person at high risk of MDR-TB should • undergo rapid testing • to start an appropriate treatment immediately • while an additional sputum specimen undergoes conventional culture and DST 27 Aims • • • • • To describe and discuss: Existing guidelines and definitions Epidemiology of MDR-TB in Europe and globally derived from surveillance and M&E (Monitoring and Evaluation) The new information on MDR-TB diagnosis The new information on MDR-TB treatment deriving from recent meta-analyses The principles of MDR-TB control, with prevention and public health aspects 28 The challenge of MDR 29 Expensive and toxic drugs are necessary 30 Grouping drugs Group 1 1st-line oral •INH Injectables •RIF •SM Fluoroquinolones •PZA •KM •Cipro •EMB •AMK •Oflox •Levo •CM •(Rfb) Group 2 Group 3 •Moxi •(Gati) Group 4 Oral bacteriostatic 2nd line •ETA/PTA •PASA •CYS Group 5 Unclear efficacy Not routinely recommended, efficacy unknown, e.g., amoxacillin/clavulanic acid, clarithromycin, clofazamine, linezolid, inmipenem/cilastatin, 31 high dose isonizid How to design a MDR-TB regimen 32 33 Metanalysis of 9,153 cases from 32 Countries • Treatment success vs. to failure/relapse, was associated with use of: • later generation quinolones, ofloxacin, ethionamide or prothionamide • use of 4 or more likely effective drugs in the initial intensive phase, and 3 or more likely effective drugs in the continuation phase. • Maximum odds of success: initial intensive phase of 7.1-8.5 months and total treatment duration of 18.6-21.5 months Changes to the recommendations on regimen composition between the 2008 and 2011 updates of WHO MDR-TB guidelines 2008 emergency update 2011 update Include at least four anti-TB drugs with either certain, or almost certain, effectiveness during the intensive phase of Tx Consider adding more drugs in patients with extensive disease or uncertain effectiveness Include at least 4 2nd -line anti-TB drugs likely to be effective as well as Z during the intensive phase of Tx The regimen should include Z and/or E one FQ, one parenteral agent and 2nd -line oral bacteriostatic anti-TB drugs (no preference of oral bacteriostatic 2nd -line anti-TB drug was made). The regimen should include Z a FQ, a parenteral agent, ethionamide (or prothionamide), and cycloserine, or else PAS if cycloserine cannot be used. No evidence found to support the use of > 4 2nd-line anti-TB drugs in patients with extensive disease. Increasing the number of 2nd -line drugs in a regimen is permissible if the effectiveness of some of the drugs is uncertain. E may be considered effective and included in the regimen E may be used but is not included among the drugs making if DST shows susceptibility up the standard regimen. Tx with Group 5 drugs is recommended only if additional drugs are needed to bring the total to 4 Group 5 drugs may be used but are not included among the drugs making up the standard regimen Intensive phase min 6 months (min 4 months after C conversion) for a total duration of min 18 months after C conversion Intensive phase min 8 months for a total duration>=20 months 35 Treatment monitoring • Treatment failure was detected best with monthly culture in MDR-TB cases. • Thus the available evidence does not support replacing monthly culture (or quarterly culture) with monthly smear 37 38 39 Consilium for MDR-TB case and programme management 40 41 4,853 C+, 361 MDR, 64 XDR MDR-TB, suscep to at least one FLD MDR-TB, resistant to all FLD XDR-TB TDR-TB (MDR+FQ+ Gr IV) 42 Eur Respir J 2007 Author Avendano Burgos Chan Chiang Cox DeRiemer Escudero Geerligs Granich/Banerjee Holts Kim(Shim) Kim(Yim) Kwon Leimane/Riekstina Lockman Masjedi Migliori Mitnick Munsiff/Li Narita ORiordan Palmero Park Perez-Guzman Quy Schaaf Shin Shiraishi Tupasi Uffredi Van Deun Yew N° Success 64 30 134 72 54 5 14 40 74 1073 432 118 85 679 128 16 17 417 127 39 19 70 60 15 79 20 353 54 97 23 440 84 N° Treated 72 45 194 125 77 47 18 43 100 2174 1288 182 129 945 218 27 83 654 671 66 28 112 131 33 157 36 535 61 159 41 603 99 Treatment Success vs Fail and Relapse and Death and Default Pooled Success = 0.54 (0.48 to 0.60) Inconsistency (I-square) = 97.4% 43 Treatment outcomes by MDR-TB patient group XDR TB (n=405) MDR-TB +FQr MDR-TB +INJr (n = 426) (n=1130) MDR-TB, susceptto FQ & Inj Total (n=4763) Pooled Outcomes (From study level meta-analysis) Success 40% (27, 53) 48% (36, 60) 56% (45, 66) 64% (57, 72) 62% (54,69) Failed/Relapse 22% (15, 28) 18% (14, 21) 12% (9, 15) 4% (2, 6) 7% (4, 9) Died 15% (8, 23) 11% (3, 19) 8% (3, 14) 8% (5, 11) 9% (5, 12) Defaulted 16% (8, 24) 12% (1,23) 16% (7, 24) 18% (12,24) 17% (11, 22) 44 Association between clinical characteristics and treatment success vs. failure/relapse/death in the different MDR-TB sub-groups Odds of success vs Characteristics failure/relapse/death Male sex (vs female)* Older age (per 10 years older)* HIV positive (vs HIV neg.)* Extensive disease (vs not)* Prior TB treatment* None FLD only FLD and SLD MDR sub-groups: † Not resistant to a FQN nor a 2nd line injectable Resistant to a second-line injectable, but not a FQN Resistant to a fluoroquinolone, but not a 2nd line injectable Resistant to both a fluoroquinolone and at least one 2nd line injectable (XDR) Pulmonary resection surgery performed (vs not) † Experienced a serious adverse event (vs not) † N 4653 6724 615 4792 aOR 1.0 0.8 0.3 0.5 (95%CI) (0.9, 1.1) (0.8, 0.9) (0.2, 0.4) (0.4, 0.6) 1275 4410 618 1.0 0.6 0.2 (Reference) (0.5, 0.8) 0.15, 0.3) 4763 1130 1.0 0.6 (Reference) (0.5, 0.7) 426 0.3 (0.2, 0.40 405 373 1511 0.2 1.5 1.0 0.2, 0.3) (0.9, 2.6) (0.8, 1.2) 45 XDR INTENS PHASE N° drugs N 0-2 24 3 47 4 5 6+ 46 36 20 (95%CI) 1.0 (reference) 1.9 (0.8, 4.3) 1.8 (0.5, 6.6) 4.9 (1.4, 16.6) N aOR 32 49 35 27 (95%CI) N 1.0 3 32 3.3 (ref) (1.3, 8.5) 6.1 (1.4, 26.3) 2.3 (0.7, 7.6) 28 17 (95%C I) N 1.0 (reference) (0.7, 3.8) 1.6 (0.3, 6.4) 1.4 (0.4, 2.9) 1.1 29 27 83 aOR 35 1.0 27 27 20 (95% CI) aOR 1.0 1.7 (95%CI) (referenc e) (0.5, 5.2) MDR-TB, susceptible to FQ & Inj N aOR 45 1.0 62 (0.5, 3.1) 165 1.1 1.3 137 1.2 (0.8, 3.8) 1.7 1.3 aOR 46 33 2.5 (ref) (0.8, 7.4) 101 3.1 (0.5, 21.1) 100 2.3 (0.7, 7.2) 1.0 12.2 3.7 3.1 (0.5, 1.8) 1.0 MDR–TB+INJr N (referenc e) (0.5, 2.3) 1.9 (0.5, 3.3) 380 120 (95%CI) (1.0, 3.7) (0.4, 3.4) 296 MDR–TB+FQr 27 5+ aOR MDR–TB+INJr 10 0-2 4 N XDR CONT PHASE N° drugs aOR MDR–TB+FQr (95%CI) (ref) (3.4, 44) MDR, susceptible to FQ & Inj N aOR 77 1.0 133 5.9 (1.7, 8.2) 239 6.0 233 4.7 (1.7, 6.0) (95%CI) (ref) (3.1, 11.0) (2.8, 13.1) 46 (2.7, 8.1) prev TX > 30 days Drug received during previous TX periods Age/ sex Country of birth 43/F IT 3 SRHEZ; FQ,Eth,AK,PAS,C,K,C yc,Rb,Clof,Dap,Cl,Th 49/F IT 3 SRHEZ; FQ,Eth,AK,PAS,C,K,C yc,Rb,Clof, Dap,Cl,Th Hospit Admis (days) SS conv (days) C conv (days) SRHEZ; FQ,Eth,AK,PAS,C,K, Cyc,Rb,Clof 422 No No Died 94 SRHEZ; FQ,Eth,AK,PAS,C,K,C yc,Rb,Clof,Dap,Cl,Th 625 No No Died 60 Drug resistance at XDR diagnosis TX dur (mo Out come First tuberculosis cases in Italy resistant to all tested drugs GB Migliori (gbmigliori@fsm.it), G De Iaco, G Besozzi, R Centis, DM Cirillo WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Care and Research Institute, Tradate Eurosurveillance 2007 47 48 XDR alone XDR+2sli XDR+sliG4† XDR+sliG4EZ n = 301 n = 68 n = 48 n =42 Cured 43 (27, 58) 30 (17, 43) 34 (-, -) 19 (0, 48)* Failed 20 (15, 25) 29 (8, 50) 33 (-, -) 26 (14, 38) Died 13 (6, 20) 18 (7, 29) 30 (18, 41)* 35 (21, 50)* Failed or died 35 (26, 45) 54 (40, 69)* 48 (-, -) 49 (37, 61) Defaulted 15 (5, 24) 15 (3, 27) 18 (-, -) 19 (6, 32) XDR-alone XDR+2sli XDR+sliG4 XDR+sliG4EZ n = 301 n = 68 n = 48 n =42 Cured 1.0 (reference) 0.4 (0.2, 0.8) 0.6 (0.2, 1.6) 0.5 (0.2, 1.7) Failed 1.0 (reference) 2.1 (1.0, 4.5) 1.8 (0.7, 4.7) 1.9 (0.7, 5.3) Died 1.0 (reference) 1.6 (0.6, 4.4) 1.7 (0.6, 4.9) 1.8 (0.6, 5.3) Failed or Died 1.0 (reference) 2.6 (1.2, 4.4) 2.6 (1.1, 6.7) 2.8 (1.0, 7.9) Defaulted 1.0 (reference) 1.0 (0.3, 2.6) 0.5 (0.2, 1.8) 0.5 (0.1, 2.0) Treatment outcome Treatment outcome 49 50 51 52 Building a regimen for XDR-TB 53 54 55 Proportion of adverse events (95% CI) Alffenaar JWC et al. [46] Anger HA/Condos R et al. [34] De Lorenzo S et al. [35] FortunJ et al. [22] Koh WJ et al. [45] Migliori GB et al. [8] Park IN et al. [44] Schecter GF et al. [30] Singla R et al. [31] Udwadia ZF et al. [32] Villar M et al. [33] Von der Lippe B et al. [43] 0 0.2 0.4 0.6 Adverse events 0.8 0.00 1.00 0.67 1.00 0.82 1.00 0.71 0.22 0.71 1.00 0.22 0.80 (0.00 - 0.37) (0.78 - 1.00) (0.09 - 0.99) (0.29 - 1.00) (0.48 - 0.98) (0.03 - 1.00) (0.29 - 0.96) (0.07 - 0.44) (0.42 - 0.92) (0.29 - 1.00) (0.03 - 0.60) (0.44 - 0.97) Pooled Proportion = 0.59 (0.49 to 0.68) Chi-square = 61.94; df = 11 (p = 0.0000) 1 Inconsistency (I 2 ) = 82.2 % Proportion of linezolid interruption due to adverse events (95% CI) Alffenaar JWC et al. [46] Anger HA/Condos R et al. [34] FortunJ et al. [22] Koh WJ et al. [45] Migliori GB et al. [8] Park IN et al. [44] Schecter GF et al. [30] Singla R et al. [31] Udwadia ZF et al. [32] Villar M et al. [33] Von der Lippe B et al. [43] 0 0.2 0.4 0.6 0.8 Linezolid interruption due to adverse events 0.00 0.87 1.00 0.82 1.00 0.40 1.00 1.00 0.54 1.00 0.70 (0.00 - 0.37) (0.60 - 0.98) (0.29 - 1.00) (0.48 - 0.98) (0.03 - 1.00) (0.05 - 0.85) (0.03 - 1.00) (0.69 - 1.00) (0.25 - 0.81) (0.03 - 1.00) (0.35 - 0.93) Pooled Proportion = 0.69 (0.58 to 0.79) Chi-square = 37.19; df = 10 (p = 0.0001) 1 Inconsistency (I2) = 73.1 % AE in Linezolid- containing regimens. Sotgiu et al, ERJ 2012 56 Meropenem (De Lorenzo S, Alffenar JW et al- ERJ 2012 in press) Cases Variables Total Cases: 37 Controlls: 61 Controls Meropenem/cla Meropenem/clavula vulanate pnate -containing sparing anti-TB value anti-TB regimen regimen -Italian cohort -Dutch cohort 16/50 (32.0) 7/32 (21.9) 9/18 (50.0) 0.04 27/48 (56.3) 20/32 (62.5) 7/16 (43.8) 0.22 37/48 (77.1) 28/32 (87.5) 9/16 (56.3) 0.02 Culture conversion at 30 days of treatment, n (%) 24/66 (36.4) 12/37 (32.4) 12/29 (41.4) 0.45 Culture conversion at 60 days of treatment, n (%) 37/62 (59.7) 24/37 (64.9) 13/25 (52.0) 0.31 Culture conversion at 90 days of treatment, n (%) 46/61 (75.4) 31/37 (83.8) 15/24 (62.5) 0.06 52.5 (38.5-65.0) 46.0 (6.0-157.0) 0.85 42.0 (28.0-65.0) 46.0 (13.0-96.0) 0.96 Sputum smear conversion at 30 days of treatment, n (%) Sputum smear conversion at 60 days of treatment, n (%) Sputum smear conversion at 90 days of treatment, n (%) Median (IQR) period from start of anti-TB therapy to sputum smear conversion, days Median (IQR) period from start of anti-TB therapy to culture conversion, days 51 (28.0-75.0) 42 (16.5-82.0) 57 Aims • • • • • To describe and discuss: Existing guidelines and definitions The epidemiology of TB and MDR-TB in Europe and globally derived from surveillance and M&E (Monitoring and Evaluation) The new information on MDR-TB diagnosis The new information on MDR-TB treatment The principles of MDR-TB control, with prevention and public health aspects 58 TB patients with inappropriate regimen have a 27fold higher risk of developing MDR-TB Multidrug resistance after inappropriate tuberculosis treatment: A meta-analysis Marieke J. van der Werf, Miranda W. Langenda, Emma Huitric, Davide Manissero ERJ 2012 in press 59 Global Policy: MDR-TB and XDR-TB 1. 2. 3. 4. 5. 6. 7. 8. Strengthen basic TB control, to prevent M/XDR-TB Scale-up programmatic management and care of MDR-TB and XDR-TB Strengthen laboratory services for adequate and timely diagnosis of MDR-TB and XDR-TB Ensure availability of quality drugs and their rational use Expand MDR-TB and XDR-TB surveillance Introduce infection control, especially in high HIV prevalence settings Mobilize urgently resources domestically and internationally Promote research and development into new diagnostics, drugs and vaccines 60 Global Policy: MDR-TB and XDR-TB 1. 2. Strengthen basic TB control, to prevent M/XDR-TB Scale-up programmatic management and care of MDR-TB and XDR-TB 3. Strengthen laboratory services for adequate and timely diagnosis of MDR-TB and XDR-TB 4. Ensure availability of quality drugs and their rational use Expand MDR-TB and XDR-TB surveillance Introduce infection control, especially in high HIV prevalence settings Mobilize urgently resources domestically and internationally Promote research and development into new diagnostics, drugs and vaccines 5. 6. 7. 8. 61 Global Policy: MDR-TB and XDR-TB 1. 2. 3. 4. 5. 6. 7. 8. Strengthen basic TB control, to prevent M/XDR-TB Scale-up programmatic management and care of MDR-TB and XDR-TB Strengthen laboratory services for adequate and timely diagnosis of MDR-TB and XDR-TB Ensure availability of quality drugs and their rational use Expand MDR-TB and XDR-TB surveillance Introduce infection control, especially in high HIV prevalence settings Mobilize urgently resources domestically and internationally Promote research and development into new diagnostics, drugs and vaccines 62 Global Policy: MDR-TB and XDR-TB 1. 2. 3. 4. 5. 6. 7. 8. Strengthen basic TB control, to prevent M/XDR-TB Scale-up programmatic management and care of MDR-TB and XDR-TB Strengthen laboratory services for adequate and timely diagnosis of MDR-TB and XDR-TB Ensure availability of quality drugs and their rational use Expand MDR-TB and XDR-TB surveillance Introduce infection control, especially in high HIV prevalence settings Mobilize urgently resources domestically and internationally Promote research and development into new diagnostics, drugs and vaccines 63 Global Policy: MDR-TB and XDR-TB 1. 2. 3. 4. 5. 6. 7. Strengthen basic TB control, to prevent M/XDR-TB Scale-up programmatic management and care of MDR-TB and XDR-TB Strengthen laboratory services for adequate and timely diagnosis of MDR-TB and XDR-TB Ensure availability of quality drugs and their rational use Expand MDR-TB and XDR-TB surveillance Introduce infection control, especially in high HIV prevalence settings Mobilize urgently resources domestically and internationally 8. Promote research and development into new diagnostics, drugs and vaccines 64 1966, the last anti-TB drug was discovered 65 Bedaquiline Delamanid 66 Carlo Forlanini, first notes on Pneumothorax January 7th, 1907 67 Interventions over time: old weapons might be useful again to manage XDR First sanatorium Germany, 1857 First Dispensary, Scotland, 1897 BCG vaccination Pneumotorax, Italy, 1907 Drugs, 1945-1962 Koch, Mtb, 1882 MMR,1950-1980 Fox:Ambulatory treatment, 1968 Styblo model, 1978 DOTS, 1991 Outbreak Management, sanatoria Risk Group Management screening drug therapy Socio-economic improvement 68 69 Pneumothorax 71 “Nobody wants me around..” 72 73 XDR and TB control: which future ? 74