Transcript and treatment outcome definitions

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
Reference
whqlibdoc.who.int/publications/2008/9789241547581_eng.pdf
2
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
3
Consultation on TB case definitions and treatment outcome
12-13 May 2011
Definitions (2)
1. Bacteriology
2. Case registration
3. Treatment outcomes
4
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
5
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 antiTB 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)
6
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
7
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
8
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
9
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
Consultation on TB case definitions and treatment outcome
10 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"
Consultation on TB case definitions and treatment outcome
11 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
Consultation on TB case definitions and treatment outcome
12 12-13 May 2011
Treatment outcomes (2)
1) Cured
2) Treatment completed
3) Died
4) Failed
5) Defaulted
6) Transferred out
Consultation on TB case definitions and treatment outcome
13 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.
Consultation on TB case definitions and treatment outcome
14 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)
Consultation on TB case definitions and treatment outcome
15 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
Consultation on TB case definitions and treatment outcome
16 12-13 May 2011
Treatment outcomes (5)
CURED : last 12 months, 5 negative cultures
PATIENT 1 Sputum
culture N
culture
N
10
Months
PATIENT 2 Sputum
22
21
Months
P
23
N
P
11
24
12
N
Consultation on TB case definitions and treatment outcome
17 12-13 May 2011
25
N
13
14
N N
P

26
N
15
N



Minimum MDR Indicators, 2010
whqlibdoc.who.int/hq/2010/WHO_HTM_TB_2010.11_eng.pdf
Consultation on TB case definitions and treatment outcome
18 12-13 May 2011
Revised R&R for MDR (1)
Indicator Group
Disaggregation
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
Consultation on TB case definitions and treatment outcome
19 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
Consultation on TB case definitions and treatment outcome
20 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
Consultation on TB case definitions and treatment outcome
21 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
Consultation on TB case definitions and treatment outcome
22 12-13 May 2011