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

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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

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Background “XDR TB”:

  • 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

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Proposal (mid-2005) “XDR TB”:

  • 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

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Objective “XDR TB”:

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

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Methods “XDR TB”:

  • “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

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Study Sample “XDR TB”:

Isolates submitted

by SRLs


Tested before 2000

(N=207) or

Tested in 2005


Isolates tested

2000 – 2004


Tested for <3 SLD



Isolates tested

for >3 SLD classes


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First-line Drug Resistance Patterns (N=17,459)

* Any except RIF

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Prevalence of Resistance to 2 (N=17,459)nd-line Drugs (isolates tested for at least 3 SLDs, %)

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Prevalence Second-line Drug Resistance (N=17,459)By Geographic Region (%)

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Patterns of 2 Geographic Region (N=3,461)nd-line Drug Resistance in MDR Isolates By Year Of Test (%)

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Limitations Geographic Region (N=3,461)

  • 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

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Conclusions and Recommendations Geographic Region (N=3,461)

  • 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

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Next Steps Geographic Region (N=3,461)

  • 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