Introduction: Host-response-based transcriptional signatures (HrTS) have been developed to identify "incipient tuberculosis (TB)". No study has reported the cost-effectiveness of HrTS for post-arrival migrant screening programs in low-incidence countries. Objectives: To assess the potential health impact and cost-effectiveness of HrTS for post-arrival TB infection screening among new migrants in the United States. Methods: We used a discrete event simulation model to compare four strategies: (1) no screening for TB infection or incipient TB; (2) 'IGRA-only', screen all with interferon gamma release assay (IGRA), provide TB preventive treatment for IGRA-positives; (3) 'IGRA-HrTS', screen all with IGRA followed by HrTS for IGRA-positives, provide incipient TB treatment for individuals testing positive with both tests; and (4) 'HrTS-only', screen all with HrTS, provide incipient TB treatment for HrTS-positives. We assessed outcomes over the lifetime of migrants entering the U.S. in 2019, assuming HrTS met the WHO Target Product Profile (TPP) optimal criteria. We conducted sensitivity analyses to evaluate the robustness of results. Results: The IGRA-only strategy dominated the HrTS-based strategies under both healthcare sector and societal perspectives, with an incremental cost-effectiveness ratio of $78,943 and $89,431 per quality-adjusted life-years (QALY) gained, respectively. This conclusion was robust to varying costs ($15 - 300) and characteristics of HrTS, and the willingness-to-pay threshold ($30,000 - 150,000/ QALY gained), but sensitive to the rate of decline in TB progression risk after U.S. entry. Conclusions: Our findings suggest that HrTS meeting the WHO TPP is unlikely to be a cost-effective component of post-arrival screening for migrants entering the U.S.

The authors have declared no competing interest.

This work was supported through grants provided by the US National Institutes of Health/ National Institute of Allergy and Infectious Diseases to NAM (R01AI146555) and the Social Sciences and Humanities Research Council of Canada Doctoral Fellowship to YLH (752-2022-0285). We declare no competing interests.

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