Status of universal drug-susceptibility testing among sputum smear-positive tuberculosis patients diagnosed at a tertiary care centre

To achieve the World Health Organization 2030 End TB targets by 20251, the government of India rolled out the Revised National TB Control Programme (RNTCP) universal drug-susceptibility testing (UDST) in 20172,3. Under UDST, the sputum smear-positive TB patients are offered two rapid molecular tests, cartridge-based nucleic acid amplification test and line probe assay to check for any drug resistance (DR). Usually, the patient turnaround time for drug-susceptibility testing (DST) is about four days4. However, after the implementation of this strategy, there is limited literature related to its evaluation5,6. The study was aimed to (i) estimate the proportion of TB-diagnosed patients who did not undergo UDST, (ii) assess the sociodemographic and morbidity-related factors associated with it, (iii) ascertain their reasons for not getting tested, and (vi) estimate the proportion with any DR.

Material & Methods

A cross-sectional analytical study was conducted among all sputum smear-positive TB patients diagnosed in the designated microscopy centre (DMC) of Jawaharlal Institute of Postgraduate Medical Education and Research, a government tertiary care centre (TCC) in Puducherry, India, between February and July 2019. Since the DR status of these patients was unknown and following the UDST strategy, all the patients were instructed to submit a sputum sample to the intermediate reference laboratory (IRL).

Patients were consecutively recruited and line-listed using the RNTCP (rechristened as National TB Elimination Programme in 2020) TB notification register maintained in DMC. Data related to NIKSHAY ID, sociodemographic profile and the presence of comorbid conditions were collected. Information regarding the outcome of drug sensitivity using the NIKSHAY ID from the TB Laboratory Register kept in IRL was extracted. The patients missing in the TB Laboratory Register, i.e. who did not submit a sputum sample for DST even after being instructed, were considered loss to follow up (drop out for UDST). These patients were contacted by telephone/mobile and were asked about the reasons for not getting themselves tested. The study was approved by the Institutional Ethics Committee and written informed consent was obtained from all patients.

Data were entered in EpiCollect5 software (centre for genomic pathogen surveillance, University department in Oxford, England, UK) and analyzed using Stata version 14 (Stata Corp. LP, College Station, TX, USA). Resistance to either rifampicin or isoniazid was considered as any DR-TB. Multivariable analysis (log-binomial model) was done to calculate the adjusted prevalence ratio (aPR) with a 95 per cent confidence interval (CI) to report association.

Results & Discussion

A total of 215 sputum smear-positive TB patients were included. The mean±standard deviation age and weight of the participants were 46.9±13.8 yr and 45.4±10.5 kg, respectively with 74 per cent (n=159) being males (Table). It was found that 34.4 per cent (n=74) (95% CI: 28.1-41.2) of sputum smear-positive TB patients did not undergo UDST, which was similar to the findings of the studies conducted in Karnataka where 33 and 34.6 per cent did not undergo UDST in 2018 and 2019, respectively6,7 which has further increased to 42 per cent2 in 2020. NIKSHAY ID at the time of sputum smear microscopy and its application to establish cohort-wise tracking will significantly decrease the attrition rate8.

Among the 141 patients who underwent UDST, 4.3 per cent (n=6) (95% CI: 1.58-9.03) had any DR; two were R resistant, two were H resistant and two had resistance to both R and H. Similar to the findings of the present study, Goyal et al9 reported a worsening trend in DR-TB in India between the two study decades (1995-2005; 2006-2015). It was estimated that 2.8 per cent of new TB patients and 14 per cent of previously treated TB patients in India were MDR-TB cases10. The estimates in the present study could be below as not all eligible patients could be tested. Thus, proper implementation of the ‘Detect-Treat-Prevent-Build’ approach in a well-constructed system is the need of the hour for the early and accurate diagnosis of DR-TB11.

In adjusted analysis, patients not undergoing UDST were significantly twice more common among TB patients aged ≤30 yr (aPR 2.36; 95% CI: 1.19-4.68) than >60 yr (Table). This could be due to the younger age group being more involved in career development than health-seeking behaviour12,13. Furthermore, as the TB burden increases with age, older age groups are more health-conscious and aware of the importance of disease treatment and its benefits14.

Of the 74 participants who did not undergo UDST, one third (n=25) could be contacted over the phone. A majority (60%, n=15) of them reported that they were not informed about DST and this was cited as the reason for not undergoing UDST. Other reasons were travel issues (24%, n=6) and the inability to produce sputum (16%, n=4). These findings re-emphasize ineffective communication by the healthcare providers to patients regarding the diagnosis and treatment procedures15. Divergence from the UDST algorithm has been found in other studies also15. However, at a sufficient scale, UDST can control MDR-TB transmission by detecting a more significant number of DR-TB cases16. Weekly monitoring of NIKSHAY ID of patient referrals between DMC and laboratories and developing a feedback mechanism to the DMC might improve testing coverage.

The study was based on the experience of a single tertiary care centre with a limited sample size and so had restricted generalizability. It is difficult to conclude the reasons for not getting tested with such a small number of interviews. Elicitation of reasons for undergoing test from participants who got the UDST done would have added advantage to the present study.

To conclude, one third of sputum smear-positive TB patients did not undergo UDST, most commonly young people; and one in 20 of those who underwent UDST had any DR-TB.