1. Overview of current MDR-TB case definitions and treatment outcome Dennis Falzon Consultation : Impact of WHO-endorsed molecular diagnostics on TB and MDR-TB case- and treatment outcome definitions WHO/HQ, Geneva, Switzerland – 12-13 May 2011

2. 2 Consultation on TB case definitions and treatment outcome 12-13 May 2011 Reference whqlibdoc.who.int/publications/2008/9789241547581_eng.pdf

3. 3 Consultation on TB case definitions and treatment outcome 12-13 May 2011 Definitions (1) -Allow different workers throughout the programme to think in the same way -Standardize the assignment of treatment to patients -Define a cohort for outcome monitoring -Make meaningful comparisons -Between projects and countries -Over time

4. 4 Consultation on TB case definitions and treatment outcome 12-13 May 2011 Definitions (2) 1. Bacteriology 2. Case registration 3. Treatment outcomes

5. 5 Consultation on TB case definitions and treatment outcome 12-13 May 2011 Bacteriology (1) -DR-TB is a laboratory definition -Laboratory needed for -diagnosis -follow-up -outcome determination

6. 6 Consultation on TB case definitions and treatment outcome 12-13 May 2011 Bacteriology (2) Mono-resistance: resistance to one anti-TB drug*. Poly-resistance: resistance to more than one anti- TB drug, other than both isoniazid and rifampicin*. Multidrug-resistance: resistance to at least isoniazid and rifampicin. Extensive drug-resistance: resistance to any fluoroquinolone, and at least one of three injectable second-line drugs (capreomycin, kanamycin and amikacin), in addition to multidrug-resistance. * For cases tested to all the "usual" anti-TB drugs (RHEZS+SLDs)

7. 7 Consultation on TB case definitions and treatment outcome 12-13 May 2011 Bacteriology (3) Sputum conversion 2 samples at least 30 days apart with negative results The date of the first set of negative tests used as the date of conversion for interim outcome, and length of the initial phase and treatment

8. 8 Consultation on TB case definitions and treatment outcome 12-13 May 2011 Case registration (1) Category IV includes : - Confirmed MDR-TB - Suspected MDR-TB: country criteria - Poly-resistant TB: certain types

9. 9 Consultation on TB case definitions and treatment outcome 12-13 May 2011 Case registration (2) 1. By previous drug use - New - Previously treated*, first-line drugs only - Previously treated*, second-line drugs * Treated for TB, for at least one month or 4-weeks

10. 10 Consultation on TB case definitions and treatment outcome 12-13 May 2011 Case registration (3) 2. By patient registration group - New - Relapse - After default - After failure of Category I - After failure of Category II - Transfer in - Other

11. 11 Consultation on TB case definitions and treatment outcome 12-13 May 2011 Case registration (4) Other - smear positive, previous history unknown - smear positive, previous history not Cat I / II - previously treated extrapulmonary - "chronics"

12. 12 Consultation on TB case definitions and treatment outcome 12-13 May 2011 Treatment outcomes (1) 1) interim outcomes : 6-months 2) definitive outcomes : 24-, 36-months - mutually exclusive - "first outcome met" principle - cured & failed defined by culture

13. 13 Consultation on TB case definitions and treatment outcome 12-13 May 2011 Treatment outcomes (2) 1) Cured 2) Treatment completed 3) Died 4) Failed 5) Defaulted 6) Transferred out

14. 14 Consultation on TB case definitions and treatment outcome 12-13 May 2011 Treatment outcomes (3) Cured: A Category IV patient who has completed treatment according to programme protocol and has at least five consecutive negative cultures from samples collected at least 30 days apart in the final 12 months of treatment. If only one positive culture is reported during that time, and there is no concomitant clinical evidence of deterioration, a patient may still be considered cured, provided that this positive culture is followed by a minimum of three consecutive negative cultures taken at least 30 days apart.

15. 15 Consultation on TB case definitions and treatment outcome 12-13 May 2011 Treatment outcomes (4) Failed: Treatment will be considered to have failed if two or more of the five cultures recorded in the final 12 months of therapy are positive, or if any one of the final three cultures is positive. (Treatment will also be considered to have failed if a clinical decision has been made to terminate treatment early because of poor clinical or radiological response or adverse events. These latter failures can be indicated separately in order to do subanalysis)

16. 16 Consultation on TB case definitions and treatment outcome 12-13 May 2011 Definition of Failed Can only be applied retrospectively Does not indicate point in time when failure occurs Change of a failing regimen not accounted for Focused primarily on bacteriology

17. 17 Consultation on TB case definitions and treatment outcome 12-13 May 2011 Treatment outcomes (5) CURED : last 12 months, 5 negative cultures Months 22 23 2425 26 Sputum culture N PATIENT 1 21 N P N NN Months 11 12 1314 15 Sputum culture P PATIENT 2 10 N N N PN  

18. 18 Consultation on TB case definitions and treatment outcome 12-13 May 2011 Minimum MDR Indicators, 2010 whqlibdoc.who.int/hq/2010/WHO_HTM_TB_2010.11_eng.pdf

19. 19 Consultation on TB case definitions and treatment outcome 12-13 May 2011 Revised R&R for MDR (1) DisaggregationIndicator Group Risk categoriesDetection (4) Children, females, HIV-positive on ARVEnrolment (4) NoneInterim results (5) HIV positive; XDR (success and death) *Final outcomes (6) * Recommended stratification as per conditions specified in instructions

20. 20 Consultation on TB case definitions and treatment outcome 12-13 May 2011 Changes (1) Separate stratifications for – Risk categories (detection) – Children (enrolment) – Females (enrolment) – HIV-positive individuals (+/- ART) (enrolment, outcome) Coverage of DSTing and DST results in risk groups No stratification of outcome by prior treatment history Separate outcomes for XDR and HIV positive where indicated Intervals (delays) in diagnosis and in start of treatment

21. 21 Consultation on TB case definitions and treatment outcome 12-13 May 2011 Changes (2) Detection & enrolment: minimum frequency Ratio of "enrolled to identified" MDR Interim outcome: just 6-month conversion of culture Outcomes : “transferred out” merged with unevaluated; information on unwarranted MDR/XDR treatment No changes in the definitions, registers or treatment card

22. 22 Consultation on TB case definitions and treatment outcome 12-13 May 2011 Acknowledgements for the Minimal MDR indicators -Working group : Dennis Falzon, Philippe Glaziou, Nico Kalisvaart, Joël Keravec, Carole Mitnick, Pierre-Yves Norval, Edine Tiemersma, Arnaud Trébucq, Francis Varaine -Substantive comments : Amal Bassili, Jaime Bayona, Salem G Barghout, Léopold Blanc, Haileyesus Getahun, Agnes Gebhard, Christian Gunneberg, Peter Metzger, Nani Nair, Norbert Ndjeka, Wilfred Nkhoma, Mamel Quelapio, Vija Riekstina, Sarah Royce, Patricia Shirey, Fraser Wares, Matteo Zignol