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2. 2 MDR- and XDR-TB: prevention, treatment and control J-P Zellweger ERS/TB PAN NET ToT, Barcelona 2010

3. 3 Objectives To familiarise with the new documents available on MDR- and XDR-TB management and with the specific components of the Stop TB Strategy To analyse the main findings on drug resistance trends, improvement of laboratory services and treatment delivery process, and the actions undertaken to tackle MDR- and XDR- TB To identify priorities and proposed solutions to further prevent the emergence of drug resistance and improve the management of MDR- and XDR- TB

4. 4 Causes of DR

5. 5 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

6. 6 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 1Drug information sheets ANNEX 2Weight-based dosing of drugs for adults ANNEX 3Suggestions for further reading ANNEX 4Legislation, human rights, and patient’s right in TB care prevention and control ANNEX 5 Use of experimental drugs outside of clinical trials ANNEX 5 Methodology

7. 7 New STB strategy and Update on XDR epidemiology

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14. 14 DOTSMDR-TB FUNDING: Government Commitment (10$/ case) > money Up to 20,000 $/ case DIAGNOSIS: SS microscopy, QA and safety measures +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

15. 15 Who needs DST? Cat I, II failures, chronics Failure anti-TB TX in the private sector Contacts of DR-/MDR-TB HCW at risk, prisoners, homeless, etc. No SS/C conversion Month 2,3 Residence in very high DR-prevalence settings Exposure to poor quality drugs Previous treatment by poor programmes Co-morbidities favouring rapid transit/ malabsorbtion HIV+ If available: for ALL TB patients!

16. 16 Algorithm for rapid DST testing

17. 17 DST testing in routine conditions

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19. 19 How to design a regimen for MDR-TB cases

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30. 30 XDR= extensively drug-resistant TB Definition Resistance to at least rifampicin and isoniazid, in addition to any fluoroquinolone, and to at least one of the three following injectable drugs used in anti-TB treatment: capreomycin, kanamycin and amikacin.

31. 31 What was known Operational definition, proposed without solid evidence SRLs’ survey on XDR-TB isolates (“ a posteriori”, no outcomes) Anecdotal description of virtually untreatable TB patients

32. 32 What was not known on XDR? Is the risk of death/ probability of success different from that of MDR? Are their clinical characteristics different? in HIV-negative patients? Is their infectiousness different? Has the XDR definition a clinical relevance? Which is the role of susceptibility to first-line drugs different from HR?

33. 33 ERS and TBNET studies contributed to answer Time to SS and C conversion double than MDR-TB Risk of death 5.5 times higher Higher failure and default rates than MDR-TB Lower success rate than MDR-TB High proportion of adverse events due to 2°-line TB drugs XDR-TB definition has both clinical and operational significance Migliori GB et al, ERJ 2007 Sotgiu et al, ERJ 2008

34. 34 Global Policy: MDR-TB and XDR-TB 1.Strengthen basic TB control, to prevent M/XDR-TB 2.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 5.Expand MDR-TB and XDR-TB surveillance 6.Introduce infection control, especially in high HIV prevalence settings 7.Mobilize urgently resources domestically and internationally 8.Promote research and development into new diagnostics, drugs and vaccines

35. Conclusions MDR/XDTR-TB is one of the major threats for the future control of TB MDR/XDR-TB is basically a man-made problem The main issues are: –Stopping the source: control of all ERRORS which sustain the creation of new cases –Accessing second-line drugs –Managing medical, human and economical problems associated with the treatment 35