1. The Patient Triage Concept: Right Diagnosis, Right Treatment
early diagnosis of patients with RR-/MDR-TB and resistance to key SLDs, followed by timely initiation of effective treatment regimens
Susan van den Hof
Liverpool
26 October 2016

2. Conflict of interest disclosure
I have no, real or perceived, direct or indirect conflicts of interest that relate to this presentation.
I have the following, real or perceived direct or indirect conflicts of interest that relate to this presentation:
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3. Patient Triage Concept: Right diagnosis, Right treatment
Rapid molecular tests for TB and resistance (FLD and SLD)
Early initiation of effective regimens for rifampicin-resistant (RR) TB patients:
Shorter regimens for RR-TB patients without
Risk or confirmed resistance to key SLD and/or
Intolerance to key SLD
Regimens containing new drugs for RR-TB patients with
Risk or confirmed resistance to key SLD
Severe TB disease
KNCV developed the patient triage concept which allows for early diagnosis of patients with RR-/MDR-TB and resistance to key SLDs, followed by timely initiation of effective treatment regimens
Effective implementation of KNCV’s patient triage concept means DR-TB patients can be offered the shorter regimen, or a regimen tailored to their needs,
applying what is known about local TB drug resistance patterns, and their own previous drug treatment and drug susceptibility test results.

4. 2016 WHO guidance underpins the Patient Triage Concept
Use of molecular line probe assays for detection of second-line drug resistance
Treatment guidelines for DR-TB
Shorter DR-TB treatment regimen (STR) recommended under eligibility criteria
Design of individualized treatment regimen uses different grouping of component medicines
Using the newly WHO recommended rapid molecular tests for second line drug resistance, patients with rifampicin resistance can be quickly triaged to the most appropriate drug-resistant TB (DR-TB) regimen, either the shorter regimen or an individualized regimen

5. Patient Triage Concept
Linking the bedaquiline donation program with introduction of the shorter DR-TB treatment regimen

6. Patient with presumptive TB Rifampicin resistant TB #
Rapid molecular test (Xpert MTB/RIF)
No TB
Rif susceptible TB
Rifampicin resistant TB #
Appropriate referral/ treatment
Standard TB treatment with First Line Drugs
# Includes patients with high risk of RR-TB such as contacts of RR/MDR-TB patients
GO THROUGH DIFFERENT OPTIONS

7. For Dx algorithm: need to consider:
ELIGIBILITY CRITERIA FOR SHORTER DRUG-RESISTANT TB TREATMENT REGIMEN
1) No confirmed resistance to fluoroquinolones (FQ) and/or second-line injectables (SLI)
2) No contact with patient that has resistance to FQ/SLI
3) No exposure to second-line drugs (SLD) for ≥ 1 month
4) No known intolerance to drugs in the shorter regimen
5) Not pregnant
6) No Extra-Pulmonary TB (EPTB)*
7) No other risk of unfavorable outcome **
Rifampicin resistant TB #
Initial treatment regimen
Shorter DR-TB treatment regimen
Eligible
Individualized DR-TB treatment regimen
Ineligible
Send sample for SL DST (genotypic and phenotypic)
START TREATMENT AFTER EVALUATION OF FOLLOWING CRITERIA:
Diagnostic algorithm designed considering laboratory capacity
of respective country
For Dx algorithm: need to consider:
Availability of SL LPA and/or SL phenotypic DST
Transport mechanisms for specimens
Information systems for transmission of results
Initiate treatment while awaiting DST result
# Includes patients with high risk of rifampicin resistance such as contacts of RR/MDR-TB TB patients
* Non-severe forms of EPTB that can be eligible for the shorter regimen include TB pleural effusion (adults and children) and TB lymph
node (children)
** Risk of unfavorable outcome includes extensive or advanced TB disease (multiple cavities or extensive parenchymal damage)

8. No resistance / intolerance Resistance / intolerance
Initial treatment regimen
Shorter DR-TB
treatment regimen
Eligible
Individualized DR-TB treatment regimen
Ineligible
Continue shorter DR-TB treatment regimen
No resistance / intolerance
to SLI and/or FQ
Change to individualized
DR-TB treatment regimen
Resistance / intolerance
to SLI and /or FQ
Continue individualized
DR-TB treatment whilst consulting experts
Regimen adjustment based on
Second-line drug susceptibility testing results
Treatment tolerance
Initiate treatment while awaiting DST result
Regimen adjustment based on
DST results
&
treatment tolerance
Patients will have been on DR-TB regimen when phenotypic DST results come in and may not be possible to switch back to 9-month regimen

9. Individualized treatment regimens for RR-TB patients ineligible for STR
Challenge TB supports inclusion of new drugs in the core DR-TB regimen for patients not eligible for the STR:
Bdq and Dlm have strong bactericidal and sterilizing activity
Efficacy confirmed in RCTs and is comparable to FLD
Tolerability of both new drugs is well documented in RCTs
WHO can not yet fully support the inclusion of new drugs as part of the core MDR-TB regimen while phase III trials are still ongoing

10. CTB/KNCV regimen design steps for RR-TB patients ineligible for STR
Choose new drug
Bdq or Dlm
STEP 2
Choose a fluoroquinolone
Lfx
Mfx
Gfx
STEP 3
Choose an injectable Km Cm Am
STEP 4
Choose other core SL agents
Pto (Eto), Cs (Trd), Lzd, Cfz
STEP 5
Choose first line drugs Z E
High-dose isoniazid 
STEP 6
Choose other add-on agents
PAS, Amx/Clv, Imp/Cln,
Meropenem, Thioacetazone
FQ or SLI depending on resistance pattern
Aim is to design a regimen with ≥5 effective TB drugs during IP

11. CTB/KNCV documents and tools to support planning and implementation of ND&Rs
Implementation planning tool
Generic programmatic and clinical guide
Generic SOPs (under development)
Generic training materials (under development)
Implementation planning tool
Assists introduction of ND&Rs by highlighting gaps in the existing processes, TA needs, and development of plans
Detailed breakdown of activities from the introductory steps to national scale-up, with tentative timelines for each step and set of activities (nationally and per site; can be done in parallel)
Generic programmatic and clinical guide
Complementary to Implementation planning tool
Follows the Patient Triage Concept: early diagnosis of patients with RR-/MDR-TB and resistance to key SLDs, followed by timely initiation of effective treatment regimens
To be adapted to the respective country setting

12. Right diagnosis, right treatment: Benefits
Patients – earlier, effective treatment with lowest possible level of side effects. Reduced costs
Health systems - shorter diagnostic delay, and less toxic, shorter and cheaper treatment, leading to better success rates
Public health - reduced transmission and reduction in creation of additional DR
early diagnosis of DR-TB, followed by timely initiation of effective treatment regimens

13. Thank you!
Acknowledgments:
Gunta Dravniece
Fraser Wares
Agnes Gebhard