Abstract
BACKGROUND: New and effective tools for detecting drug-resistant tuberculosis (DR-TB) include GeneXpert XDR and targeted Next Generation Sequencing (tNGS). However, data on their implementation in high TB-burden settings is limited. We aimed to determine cost-effectiveness of different strategies using GeneXpert XDR or tNGS for DR-TB detection in high TB-burden, low-resource settings. METHODS: A dynamic simulation model was calibrated to WHO-reported TB data for Philippines and Thailand. Intervention scenarios for expanded diagnostic testing of drug-resistance were simulated for 2025 - 2035. Health benefits were estimated using disability-adjusted life years. Cost-effectiveness was calculated from a health system perspective using country-level TB diagnosis and treatment costs. Analyses include incremental cost-effectiveness ratios (ICERs) and incremental net monetary benefit (INMB). RESULTS: Implementing GeneXpert XDR or tNGS for DR-TB detection improves TB health outcomes. Scenarios using GeneXpert XDR are more likely to be cost-effective than scenarios using tNGS. Interventions targeting previously treated cases reduce costs but also reduce health benefits. Testing all TB cases with GeneXpert XDR is cost-effective (Philippines ICER = $1,808, INMB = $210M; Thailand ICER = $5,251, INMB = $26M) with a 1 x GDP willingness-to-pay threshold (WTP). Targeting GeneXpert XDR to previously treated cases is also cost-effective (Philippines ICER = $1,288, INMB = $52M; Thailand ICER = $3,667, INMB = $9.2M) but results in lower INMB. tNGS is cost-effective at higher WTP. INTERPRETATION: In high TB-burden countries, GeneXpert XDR is cost-effective as an additional DR-TB diagnostic test. tNGS is not cost-effective for routine clinical DR-TB testing but has potential for application to high-risk populations, especially with introduction of new TB treatment regimens.