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Do we need to test for isoniazid resistance?

Do we need to test for isoniazid resistance?. No conflict of interest. Claudia Denkinger, MD PhD McGill University, Montreal Foundation for Innovative New Diagnostics. Context. Niemz Exp Rev Mol Diag 2012 Menzies PLOS Med 2009 Jacobson CID 2011 Smith IJTLD 2012.

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Do we need to test for isoniazid resistance?

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  1. Do we need to test for isoniazid resistance? No conflict of interest Claudia Denkinger, MD PhDMcGill University, Montreal Foundation for Innovative New Diagnostics

  2. Context NiemzExp Rev MolDiag 2012 Menzies PLOS Med 2009 Jacobson CID 2011 Smith IJTLD 2012 Xpert rapidly being rolled Xpert includes RIF but not INH resistance testing INH resistance is much more common than MDR Treatment of INH resistant MTB with 1st line drugs is associated with increase failure/relapse rates and increased development of MDR

  3. ??? Should the next generation of molecular tests include detection of isoniazid resistanceto prevent • A further increase in INH resistance • INH resistance driving MDR resistance

  4. Susceptible Latent TB Infection Primary progression Primary progression New active TB - Access to diagnostics New active TB – No access to diagnostics Secondary progression Secondary progression Self cure Failure Treated/Cured Failing on therapy Cured Default/Relapse Previously treated active TB – Access to diagnostics Cured Default/Relapse Reinfection Failing on 2nd line or DST- guided treatment Cured with 2nd line or DST guided treatment

  5. Model Year 0 Equilibrium Implementation of tests Steady state (60 years ago) Rise of MDR and INH over 60 years to levels reported today (2.1%, 15%) for epidemiological setting like India Standard diagnostic, calibrated to CDR (~75%) Molecular testing: 95% sensitivity MDR Rx at baseline only for pts failing 1st line Rx WHO Global report 2012

  6. Input parameters WHO Global report 2012 Menzies PLOS Med 2009 Jacobson CID 2011

  7. Scenarios with molecular test • TB detection only • Rif detection • INH +RIF detection • Low coverage: 15%, 25%, 30% > new, relapse/default, failure • High coverage: 50%, 80%, 100% > new, relapse/default, failure WHO Global report 2012

  8. A B D C

  9. Sensitivity analysis TB+RIF/INH vs TB+RIF 0.2 0 0.2

  10. Conclusions • INH testing in addition to rifampin resistance detection does not have a substantial effect • on INH resistance • or MDR-TB • Testing for rifampin resistance in contrast has a sizeable effect on MDR • Idealized scenario • Reduction in prevalent (chronic) cases early on • Reduction in time to diagnosis as MDR

  11. Limitations Smith IJTLD 2012 Balcells EID 2006 WHO Report 2012 RNTCP 2011 Simplified model Not including HIV limits generalizability Not considering IPT > limited use, unclear impact on resistance Not considering different health sectors Not accounting for possible beneficial effects of detection of rifampin monoresistance

  12. Supplementary Figures

  13. A B Figure S1 C D

  14. A B Figure S3 C D

  15. A B Figure S5 C D

  16. Thank you! Questions???

  17. Acknowledgement David Dowdy Madhu Pai Dick Menzies

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