Cost-effectiveness of targeted next-generation sequencing (tNGS) for detection of tuberculosis drug resistance in India, South Africa and Georgia: a modeling analysis

Suvesh Shrestha; Angelina Addae; Cecily Miller; Nazir Ismail; Alice Zwerling

doi:10.1016/j.eclinm.2024.103003

Cost-effectiveness of targeted next-generation sequencing (tNGS) for detection of tuberculosis drug resistance in India, South Africa and Georgia: a modeling analysis

EClinicalMedicine. 2024 Dec 24:79:103003. doi: 10.1016/j.eclinm.2024.103003. eCollection 2025 Jan.

Authors

Suvesh Shrestha¹, Angelina Addae¹, Cecily Miller², Nazir Ismail^{2

3}, Alice Zwerling¹

Affiliations

¹ School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada.
² Global Tuberculosis Program, World Health Organization, Geneva, Switzerland.
³ Department of Clinical Microbiology and Infectious Diseases, Faculty of Health Sciences, Wits University, Johannesburg, South Africa.

Abstract

Background: Targeted next-generation sequencing (tNGS) is promising alternative to phenotypic drug susceptibility testing (pDST) for detecting drug-resistant tuberculosis (DRTB). This study explored the potential cost-effectiveness of tNGS for the diagnosis of DR-TB across 3 settings: India, South Africa and Georgia.

Methods: To inform WHO guideline development group (GDG) on tNGS we developed a stochastic decision analysis model and assessed cost-effectiveness of tNGS for DST among rifampicin resistance individuals. We also assessed tNGS as initial test for TB drug resistance in bacteriologically confirmed TB. Diagnostic accuracy and cost data were sourced from a systematic review conducted for GDG, covering studies published until September 2022. The primary outcome was incremental cost (2021 US$) per disability-adjusted life year (DALY) averted.

Findings: tNGS when compared with in-country DST, tNGS proved cost-effective in South Africa (ICER: $15,619/DALY averted, WTP: $21,165) but not in Georgia (ICER: $18,375/DALY averted, WTP: $15,069). In India, tNGS dominated in-country DST practice, providing greater health impact at lower cost. When comparing tNGS with universal pDST, tNGS was dominated by pDST in all three countries. In Georgia, using tNGS as initial test for TB drug-resistance compared to Xpert MTB/Rif followed by pDST appeared cost-effective. Scenario with 50% reduction in tNGS test kit costs made tNGS cost-effective across all three countries, while a high Bedaquiline resistance prevalence (30%) led to a worsening cost-effectiveness.

Interpretation: tNGS may be cost-effective in India, South Africa and Georgia when comprehensive DST is not routinely performed. Thus, existing DST practice and healthcare infrastructure should be considered before implementation and scale-up of tNGS.

Funding: Global Tuberculosis Program, World Health Organization (2022/1249364-0).

Keywords: Cost-effectiveness analysis; Disability-adjusted life year (DALY); Drug-resistant tuberculosis (DRTB); Incremental cost-effectiveness ratio (ICER); Targeted next-generation sequencing (tNGS).