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Extensive Second-line Drug Resistance in Tuberculosis - “XDR TB”: Global Survey of Supranational TB Reference Laboratories.

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  1. Extensive Second-line Drug Resistance in Tuberculosis - “XDR TB”:Global Survey of Supranational TB Reference Laboratories Sarita Shah1, Abigail Wright A2, Fadila Boulahbal3, Chris Gilpin3, Francis Drobniewski3, Gill-Han Bai3, Marta Havelková3, Rosario Lepe3, Beverly Metchock3, Maria Filomena Rodrigues3, Françoise Portaels3, Armand Van Deun3, Sabine Rüsch-Gerdes3, Véronique Vincent3, Lucia Barrera3, Kayla Laserson1, Charles Wells1, Peter Cegielski1 1CDC Atlanta, 2WHO Geneva, 3Supranational TB Reference Laboratory Network

  2. Background • Green Light Committee (GLC) evaluates and monitors DOTS-Plus projects world wide, ~60 to date, 35 approved in 29 countries, ~12,000 patients • Increasing anecdotal reports of TB resistant to virtually all 2nd-line drugs (SLDs) • Informal consultation with several Supranational TB Reference Laboratory (SRL) directors • Confirmed similar observations • Supported a collaborative project to count these cases

  3. Proposal (mid-2005) • Collaboration with WHO and SRL network to count cases of TB with extensive resistance to SLDs • Reputation of SRLs minimize questions of validity of 2nd-line DST results • Global geographic distribution • Many SRLs are (national) reference labs (NRLs) in their own countries • In addition to QA for global DRS, many SRLs assist NRLs world wide • SRLs history of working together

  4. Objective • To assess the extent to which extensive resistance to SLDs has begun to emerge among MDR Mycobacterium tuberculosis (Mtb) isolates in the SRL network

  5. Methods • “XDR TB” defined as MDR TB that also has resistance to ≥3 of 6 major classes of SLDs (tested) • All SRLs invited to contribute data on Mtb isolates tested for resistance to at least 3 major classes of SLDs, 2000-2004 • 17 of 23 SRLs agreed to participate, 12 sent data in time for 2005 IUATLD • SLD resistance patterns analyzed by year, region, and 1st line drug resistance pattern

  6. Study Sample Isolates submitted by SRLs (N=18,215) Tested before 2000 (N=207) or Tested in 2005 (N=14) Isolates tested 2000 – 2004 (N=17,994) Tested for <3 SLD classes (N=535) Isolates tested for >3 SLD classes (N=17,459)

  7. Geographic region from which cultures were received by SRLs (N=17,459)

  8. First-line Drug Resistance Patterns * Any except RIF

  9. Prevalence of Resistance to 2nd-line Drugs (isolates tested for at least 3 SLDs, %)

  10. 2nd-line Drug Resistance Patterns

  11. Prevalence Second-line Drug ResistanceBy Geographic Region (%)

  12. Patterns of Second-line Drug Resistance in MDR Isolates by Geographic Region (N=3,461)

  13. Patterns of 2nd-line Drug Resistance in MDR Isolates By Year Of Test (%)

  14. Limitations • Variation in methods and results for SLD testing • No standards for QA for SLD susceptibility testing • Limited reproducibility of DST for certain drugs • Sampling bias • Convenience sample does not represent a specific geographic region or patient population • No true denominator; not possible to determine case rates, only case counts • Differing indications for SLD testing (all patients, failures/retreatment cases, only MDR isolates) • Different and minimal patient data available to each SRL limited comparisons

  15. Conclusions and Recommendations • Extremely drug-resistant “XDR” TB has emerged in all continents • XDR strains may be • More prevalent in regions with high rates of MDR TB • Increasing over time • Imperative to prevent, treat TB & MDR TB more effectively • Population-based data needed to estimate current magnitude of XDR TB and monitor trends • QC/QA standards for 2nd-line DST needed to help ensure global reproducibility

  16. Next Steps • SRLs that agreed to participate but have not yet sent data or only part of data (< 5 years) please send data a.s.a.p. • Finalize analysis, draft manuscript, rapid submission • Prepare advocacy, publicity strategy • Plan population-based survey and/or prospective study

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