Is targeted next generation sequencing for drug-resistant tuberculosis feasible in a high-burden setting: a...

Targeted next-generation sequencing (tNGS) offers promise in the rapid detection of drug-resistant tuberculosis (DR-TB) directly from sputum. While pilot studies on tNGS are emerging, there is limited empirical qualitative evidence on tNGS implementation. This study, therefore, aimed to explore the experiences of tNGS programmatic implementation by clinicians, laboratory technicians and policymakers to identify perceived key operational barriers and enablers.

An exploratory qualitative study employing inductive thematic analysis. Data were collected via semi-structured interviews and focus group discussion. Analysis was guided by the theoretical framework of acceptance.

This study was conducted between March and October 2025 as part of a broader implementation study evaluating tNGS potential programmatic integration in West Java, Indonesia. Participants were recruited from a DR-TB reference laboratory and a tertiary care hospital.

A purposive sample of 18 tNGS users participated, including clinicians (n=7), laboratory technicians (n=9) and policymakers (n=2).

Analysis revealed a dual challenge for tNGS implementation: technical-operational complexity and unguided clinical utility. Technical barriers include laboratory workflow optimisation and the need for highly skilled technicians for routine operation. From a clinical point of view, lack of local tNGS guidelines for clinicians and absence of local evidence such as cost-effectiveness and diagnostic performance at the policy levels hampered clinical adoption. Several enablers for tNGS implementation were identified, namely technicians with prior sequencing experience, perceived clinical value for complicated cases and advocacy within professional networks.

Successful scale-up of tNGS for DR-TB in high-burden settings requires a coordinated multisectoral strategy. Generating local evidence on robust laboratory data for technical guidelines, clinical utility and cost-effectiveness are warranted to support tNGS adoption. This evidence can then be integrated into the national tNGS roll-out strategy to enable sustainable and nationwide adoption of tNGS.