Overview of current MDR-TB case definitions and treatment outcome Dennis Falzon Consultation :...

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 Consultation on TB case definitions and treatment outcome12-13 May 2011

Reference

whqlibdoc.who.int/publications/2008/9789241547581_eng.pdf


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


Definitions (2)

1. Bacteriology

2. Case registration

3. Treatment outcomes


Bacteriology (1)

- DR-TB is a laboratory definition

- Laboratory needed for

- diagnosis

- follow-up

- outcome determination


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)


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


Case registration (1)

Category IV includes :

- Confirmed MDR-TB

- Suspected MDR-TB: country criteria

- Poly-resistant TB: certain types



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



2. By patient registration group- New

- Relapse

- After default

- After failure of Category I

- After failure of Category II

- Transfer in

- Other



Other

- smear positive, previous history unknown

- smear positive, previous history not Cat I / II

- previously treated extrapulmonary

- "chronics"


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



1) Cured

2) Treatment completed

3) Died

4) Failed

5) Defaulted

6) Transferred out



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.



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)


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



CURED : last 12 months, 5 negative cultures

Months 22 23 24 25 26

Sputumculture N

PATIENT 1

21

N P N N N

Months 11 12 13 14 15

Sputumculture P

PATIENT 2

10

N N N P N


Minimum MDR Indicators, 2010

whqlibdoc.who.int/hq/2010/WHO_HTM_TB_2010.11_eng.pdf


Revised R&R for MDR (1)

Indicator GroupDisaggregation

Detection (4)Risk categories

Enrolment (4)Children, females, HIV-positive on ARV

Interim results (5)None

Final outcomes (6)HIV positive; XDR (success and death) *

* Recommended stratification as per conditions specified in instructions


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


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


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

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