Detecting drug resistance at the

time of TB diagnosis
Dr Sarabjit Chadha
The Union

Drug resistance TB
Resistance to anti-TB drugs
MDR TB resistance to Rifampicin and Isoniazid
XDR TB MDR TB plus resistance to quinolones and
second line injectables
Poor treatment outcomes

Burden of MDR TB
Globally* Annually 3.5% of new; 20% of previously
treated TB cases have MDR TB
~480,000 MDR cases annually

Annually ~210,000* deaths occur due to MDR- TB

* WHO Global TB Report 2014

Patient presents with symptoms of TB

Smear microscopy X ray
(Drug resistance usually not tested)
Diagnosed as TB and initiated on treatment
for drug sensitive TB (6 mths)

Cured
Delay of ~12 months before diagnosis of
drug resistance
Most of the patients will not survive the
delay and inappropriate treatment
especially if there are co-morbidities like
HIV, Diabetes
The prolonged suffering (and maybe
death) can be avoided if testing for DRTB is done early

Fails treatment; put on retreatment regimen (8 mths)

(Drug resistance not tested)
Fails treatment again
Tested for drug resistance

Treated for DR-TB

Why early diagnosis of DR-TB is important ?

Patient is given inappropriate treatment
Prolongs suffering and morbidity
Enhances severity of disease- mortality
Amplify resistance (more difficult to treat)
Treatment interruption
Seek alternate care
Transmission to others continues

Most of these are avoidable if diagnosis is

made early and appropriate treatment given

Reasons for delay and changing scenario

Smear microscopy does not detect resistance
Earlier the only option was culture and DST
3-4 months to give results
Requires laboratory infrastructure and skilled workers
Funds and political commitment

Newer rapid molecular tests the situation has changed

Xpert MTB/RIF (CBNAAT)

Results in less than 2 hours
Automated
No special infrastructure required
Diagnose both TB and Rifampicin resistance together

India- Case study

Highest TB and MDR TB burden globally
2% of new and 15% of those with previous
history of TB are MDR TB*
~62000 MDR cases annually

Initiated MDR-TB services in 8 districts in 2007

(20 m pop)
Expanded to the entire country (700 districts) in
2013 (1.2 billion pop)
Starting with 4 labs in 2007 there are today
62 labs with culture & DST facilities
50 with Line Probe Assay
89 Xpert MTB/RIF (CBNAAT) sites
* WHO Global TB Report 2014

Progress 2007-2014
50 LPA
89 Xpert
69 CDST labs

300000

18 LPA
18 Xpert
36 CDST labs

250000

200000

30000

25562
25000

255408

9 CST labs

20000

4 CDST labs
150000

15000

100000

10000

4297
50000

5000

2341
109 309
2007

17696

8144
2008

2009

Number tested for MDR-TB

0
2010

2011

2012

Diagnosed as MDR TB

2013

2014

Initiated on treatment

Plan ahead
Universal DST for all TB cases by 2019

Ambitious plan
Set up 120 culture and DST labs
950 CBNAAT (Xpert or similar technology) sites
Over 1 million DST annually
Provide testing for second line drug resistance

Treatment for all diagnosed

at least 60,000 MDR cases annually

Improving treatment outcomes

Currently ~50% to 65%

Saving additional lives

Moving towards early diagnosis of DR-TB

2007

4 Culture and DST laboratories

Failures of retreatment cases

2011

36 labs; 18 LPA; 18 Xpert (CBNAAT) sites

All Failures; PLHIV, contacts of MDR TB

2014

62 labs; 50 LPA; 89 Xpert (CBNAAT) sites

All failures, All retreatment cases, PLHIV, contacts MDR

2019

120 labs; 950 Xpert (CBNAAT) sites

All TB cases tested for drug resistance at diagnosis
All MDR cases tested for second line drug resistance

Challenges
Cost of the Xpert MTB/RIF machines (~20,000 $) and cost per
test is still high (10 $)
Additional funds and political commitment

Diagnosis of resistance to second line drugs

pre- XDR and XDR TB)
Currently by liquid culture which require accredited labs
No automated convenient tests like Xpert available

Matching treatment capacity

Enhance treatment adherence
Psycho-social-economic support
Shorter drug regimens

Prevention of MDR TB

Thank you