On occasion of World Tuberculosis Day, the report of India’s first Nationally representative Anti-Tuberculosis Drug Resistance Survey (2014-2016) was released.

Background Information and Rationale:

India has more new tuberculosis (TB) patients annually than any other country globally, contributing to 27% of the world’s TB burden. About 2.79 million TB patients are estimated to be added annually.

The Revised National Tuberculosis Control Programme (RNTCP) notified around 1.94 million TB patients in 2016.

As per the Global TB Report 2017, worldwide approximately 4.1% of new TB patients and
19% of previously treated TB patients have multidrug resistant-TB (MDR-TB), i.e. TB
resistant to at least two of the first-line drugs – isoniazid and rifampicin.

Extensively drug resistant TB (XDR-TB), defined as MDR-TB with additional resistance to at least one fluoroquinolone and one second line injectable drug, has been reported by 123 countries.

The proportion of XDR-TB among MDR-TB patients is 6.2% worldwide. The estimated
number of MDR/rifampicin resistant (RR)-TB in India is 147 000, accounting for one fourth of the global burden of MDR/RR-TB.

The treatment success rate among MDR-TB patients in India is consistently about 46% and the death rate is around 20%, as against the global level of treatment success rate of 52% and death rate of 17%. High rates of treatment failure and deaths are associated with fluoroquinolone resistance in the Indian cohort of MDR-TB patients.

India has sub-national data from state level anti-TB drug resistant surveys conducted in the past; However the epidemiology of DR-TB in India has never been studied nationally.

Key Messages:

This is the largest ever National Drug Resistance Survey (NDRS) conducted by any country in the world and the first ever survey having drug susceptibility testing (DST) for 13 anti-TB drugs using the automated liquid culture system, mycobacteria growth indicator tube (MGIT) 960®.

Methodology:

The sampling strategy in this survey was a single-stage, weighted cluster sampling method, in which clusters were selected with probability proportional to size, with each cluster contributing a fixed number of new and previously treated TB patients.

The primary sampling unit in the survey was the RNTCP-defined Tuberculosis Unit (TU) and survey participants were recruited from all Designated Microscopy Centres (DMCs) in the selected TUs. Each TU represented a cluster. The proportion of urban TUs in the selection was 24%.

Once TUs were selected, all DMCs in the selected TU would contribute until the enrolment of cumulative number of expected patients reached the required
sample size. A total of 44 consecutive sputum smear-positive TB patients diagnosed at the DMCs from each selected TU were recruited to include 27 new TB patients and 17 previously treated TB patients per TU. Based on this, the total new and previously treated TB patients were rounded off to 3280 and 2040.

Those patients who met the inclusion criteria but could not be included in the survey for
various reasons were replaced by consecutive patients diagnosed in the DMCs of the same TU according to the sampling procedure described.

Two sputum specimens from each study patient were decontaminated using N-acetyl-L-cysteine–sodium citrate–sodium-hydroxide (NALC-NaOH) procedure. Microscopy using auramine-O-phenol of the concentrated deposit smear was performed and inoculated onto 7 ml MGIT tubes as per the MGIT 960 System Manual and RNTCP Laboratory manual. Back up cultures for both specimens were maintained on LJ medium. One specimen was inoculated per tube. Tubes identified as positive by the MGIT system were further identified as M. tuberculosis-complex by using immune-chromatographic tests. Drug Susceptibility Testing (DST) was performed on only one positive-culture after identification as M. tuberculosis using the modified proportion sensitivity method for liquid culture system.

Results:

• MDR-TB is 6.19% (CI 5.54–6.90%) among all TB patients
  New patients: 2.84% (CI 2.27–3.50%)
  Previously treated TB patients: 11.60% (CI 10.21–13.15%).
• Among MDR-TB patients, additional resistance
  to any fluoroquinolones: 21.82% (17.33–26.87%), and
  to any second-line injectable drugs: 3.58% (1.8–6.32%).
• Among MDR-TB patients, additional resistance to at least one drug from each of the two classes, i.e. fluoroquinolone and second-line injectable drugs (XDR-TB) was 1.3% (0.36–3.30%).
• Any first- or second line drug resistance among all TB patients is 28.0% (CI 26.77–29.29%)
  New patients: 22.54% (CI 21.10–24.10%)
  Previously treated TB patients: 36.82% (CI 34.64–39.04%).
• Any isoniazid resistance is
  New patients: 11.06% (CI 9.97–12.22%)
  Previously treated TB patients: 25.09% (CI 23.1–-27.11%).
• Any pyrazinamide resistance is
  New patients: 6.95% (CI 6.07–7.91%)
  Previously treated TB patients: 8.77% (7.53–10.13%).

MDR-TB rates at the national level are still within the range of previous state-level surveys conducted in India. However, more than a quarter of TB patients in India have drug resistance to one or the other anti-TB drug.

Fluoroquinolone resistance among MDR-TB patients is high and is similar to resistance rates reported by the RNTCP.

The survey results clearly indicate that drug resistance is present in all settings, and the wide range of resistance patterns from any isoniazid resistance to XDR-TB needs to be addressed with strengthening of drug resistance surveillance, universal DST and appropriate DST guided treatment strategies. 

Useful Links:

Link to the Central TB Division website of Government of India:

https://tbcindia.gov.in/index.php

Link to the Report of the first National Anti-TB Drug-Resistance Survey (English) [PDF]:

https://tbcindia.gov.in/showfile.php?lid=3315

Link to India TB Report 2018 (RNTCP’s Annual Status Report) (English) [PDF]:

https://tbcindia.gov.in/showfile.php?lid=3314