Emergence and Global Spread of Extensive Drug Resistance in Tuberculosis: "XDR-TB" Study
Comprehensive study on the global emergence of extensively drug-resistant tuberculosis (XDR-TB) based on data from Supranational TB Reference Laboratories, highlighting trends from 2000 to 2004 and recommendations for effective prevention and treatment.
Emergence and Global Spread of Extensive Drug Resistance in Tuberculosis: "XDR-TB" Study
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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
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
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
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
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
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)
Geographic region from which cultures were received by SRLs (N=17,459)
First-line Drug Resistance Patterns * Any except RIF
Prevalence of Resistance to 2nd-line Drugs (isolates tested for at least 3 SLDs, %)
Prevalence Second-line Drug ResistanceBy Geographic Region (%)
Patterns of Second-line Drug Resistance in MDR Isolates by Geographic Region (N=3,461)
Patterns of 2nd-line Drug Resistance in MDR Isolates By Year Of Test (%)
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
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
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