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  1. 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

  2. MDR-TB management: what is new? GB Migliori WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Tradate Italy

  3. 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

  4. 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

  5. 2000

  6. Guidelines for the programmatic management of drug-resistant tuberculosis (1) 1Background 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 ANNEX 5 Methodology

  8. Causes of DR

  9. Causes of MDR Patient mismanagement

  10. Definitions • Mono-R • Poly-R • MDR • XDR • SS+, C+ • Cure, failure • Treatment monitoring

  11. XDR= extensively drug-resistant TBDefinition 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.

  12. XDR= HR + 1 FQ + 1 Injectable (KM or AMK or CM) 1st-line oral Injectables • INH • RIF • PZA • EMB • (Rfb) Fluoroquinolones • SM • KM • AMK • CM Oral bacteriostatic 2nd line • Cipro • Oflox • Levo • Moxi • (Gati) Unclear efficacy • ETA/PTA • PASA • CYS Not routinely recommended, efficacy unknown, e.g., amoxacillin/clavulanic acid, clarithromycin, clofazamine, linezolid, inmipenem/cilastatin, high dose isonizid

  13. 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

  14. Estimatedabsolute numbers of reported cases with MDR-TB* <100 100–999 1000–9999 >10,000 *among reported pulmonary TB patients

  15. Distribution of MDR-TB among new TB cases, 1994-2010.

  16. Distribution of MDR-TB among previously treated TB cases, 1994-2010.

  17. Indicates survey data reported in an earlier phase of the project Top 19 settings with MDR among new cases > 6% (1994-2007)

  18. The highest proportions of MDR-TB ever reported in a survey have recently been found in Minsk, the capital city of Belarus: • 35.3% (95%CI: 27.7-42.8) in new pts • 76.5% (95%CI: 66.1-86.8) in previously treated pts The new MDR-TB world record

  19. 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 Global Plan target ~270,000 in 2015 290,000 53,000 19,000

  20. Proportion of TB patients tested for MDR-TB remains low New cases Previously treated Global plan target for 2015 = 20% Global plan target for 2015 = 100%

  21. Scale-up of MDR-TB treatment vs. Global Plan targets 2007 2008 2009 2010 2011 2012 2013 2014 2015

  22. Trend of MDR-TB among new cases, Estonia, Latvia and…Tomsk Oblast, RF Estonia Latvia Tomsk oblast, RF TB notification rate % MDR among new

  23. Countries that had reported at least one XDR-TB case by Oct 2011

  24. 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

  25. 20/36 HBCs* have insufficient capacity to diagnose MDR-TB Culture and DST laboratories per 5M, 2010 ≥1 <1 *HBC= high-burden country 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

  26. Traditional view: 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+

  27. 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+ • ALL CASES??

  28. The “magic” Gene Xpert

  29. Roll-out of Xpert MTB/RIF As of 30 September 2011 GeneXpert ordered – 40 countries 105 countries eligible for concessional prices, no order yet Not eligible for concessional pricing Source: FIND; more info at: www.who.int/tb/laboratory/mtbrifrollout

  30. 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

  31. 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

  32. The challenge of MDR

  33. Expensive and toxic drugs are necessary

  34. Grouping drugs Group 1 1st-line oral Group 2 Injectables • INH • RIF • PZA • EMB • (Rfb) Group 3 Fluoroquinolones Group 4 • SM • KM • AMK • CM Oral bacteriostatic 2nd line Group 5 • Cipro • Oflox • Levo • Moxi • (Gati) Unclear efficacy • ETA/PTA • PASA • CYS Not routinely recommended, efficacy unknown, e.g., amoxacillin/clavulanic acid, clarithromycin, clofazamine, linezolid, inmipenem/cilastatin, high dose isonizid

  35. How to design a MDR-TB regimen

  36. 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

  37. Changes to the recommendations on regimen composition between the 2008 and 2011 updates of WHO MDR-TB guidelines

  38. 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

  39. GLC: advantages for projects • Access to quality-assured drugs • Access to low-cost drugs • Access to a continuous drug supply • Access to technical assistance • Access to an external monitoring mechanism • Increased rational use of drugs • Creation of wide evidence base for policy development

  40. Estonia % of NTP budget spent on second line drugs 1998-2000

  41. MDR treatment programmeDecentralised case management Centralised • Registration • Establishment of treatment • Monitoring • Data management • Supervision Decentralised case management • Case finding • Case management • in specialized MDR-TB hospitals • in district TB department, at home, at family physician • Ensure adherence • Record keeping Consilium for MDR-TB case and programme management

  42. Latvia, Side Effects - Cohort 2000 • 86% of patients experienced side effects • Median of 4 side effect reports per person • Most common side effects • Nausea 73.0% • Vomiting 38.7% • Abdominal pain 38.2% • Dizziness 35.8% • Hearing problems 28.4% • 61% changed or discontinued drugs during treatment owing to side effects • 2 patients stopped treatment due side effects

  43. Results: Final Conversion Over Time N = 129 patients who converted, Latvia