IGRA Gains Ground as Ontario Weighs Latent Tuberculosis Screening Strategy
Interferon-gamma release assay testing is emerging as a more precise way to screen for latent tuberculosis infection in the populations where the test is meant to be used, and Ontario’s health technology assessment places the assay on firm ground. The review compared IGRA with the traditional tuberculin skin test across diagnostic accuracy, cost-effectiveness, budget impact, and clinician preferences, then mapped the findings to provincial screening decisions. In practice, the central question is not whether latent TB matters — it does — but which test is most likely to identify the right patients without sending large numbers of people into unnecessary follow-up care.
The review’s clinical message is straightforward. IGRA performs well as a rule-in test because specificity remains consistently high, which means fewer false-positive results than with TST. In tuberculosis screening, false positives are not a minor nuisance; they can trigger follow-up visits, imaging, treatment discussions, and anxiety in patients who may never have needed any of it. A test with higher specificity has particular value in settings where prior BCG vaccination can blur the signal from skin testing.
High Specificity, With Performance Shaped by Immune Status
Evidence from 12 systematic reviews, representing more than 500 unique primary studies, supported IGRA use in the settings described by the Canadian TB Standards. Across the reviews, IGRA generally showed good diagnostic accuracy, but performance was not uniform across all populations. Sensitivity was somewhat lower in people with underlying immunosuppression, including those living with HIV, organ transplant recipients, people receiving cancer treatment, and patients on dialysis. In those groups, a negative result cannot be treated as a clean bill of health, because impaired immune responses can blunt test reactivity.
One practical feature of IGRA stood out in this review: indeterminate results can signal the need for additional clinical evaluation. In immunocompromised patients, that is often more informative than a misleadingly reassuring negative skin test. The biological logic is clear. When immune function is altered, the immune readout becomes less stable, and the assay can reveal uncertainty rather than hiding it.
Head-to-head comparisons with TST also pointed in the same direction. Among people who tested positive on both assays, the lower risk difference of developing active TB suggests that IGRA is less likely than TST to label low-risk individuals as infected. The pattern was especially notable in immunocompromised populations, but it also appeared in children, older adults in nursing homes, and people with prior BCG vaccination. For screening programs, this is not a trivial distinction. It changes who gets labelled, who gets evaluated, and who may be exposed to treatment that was never necessary.
Cost-Effectiveness Favours Targeted Use in High-Risk Groups
Economic evidence from five Canadian studies, all judged to be of good quality, reinforced the clinical findings. In high-risk populations aligned with the Standards, IGRA was cost-effective or cost-saving compared with TST alone, whether used as a standalone test or in a sequential pathway after TST. Three studies were directly applicable to Ontario, which allowed the assessment to avoid a new primary economic evaluation and instead rely on evidence already grounded in the public payer setting.
The budget impact analysis brought the most immediate policy consequences into view. Over five years, publicly funding IGRA in all examined subpopulations would add between $2.99 million with IGRA alone and $18.80 million with sequential pathways that include TST. Those totals mask substantial differences between populations. In BCG-vaccinated immigrants and BCG-vaccinated people identified through contact investigations, the analysis estimated savings of $1.63 million or more over five years. The savings came from fewer follow-up evaluations and less unnecessary treatment, alongside prevention of reactivated infection in people correctly identified as infected.
The opposite pattern appeared in immunocompromised populations, where publicly funded IGRA was associated with about $6.26 million or more in additional costs over five years. Those costs arose because more people who had previously been missed by TST would undergo appropriate medical evaluation. When the model assumed a high chance of latent TB reactivation in immunocompromised populations, IGRA shifted into cost-saving territory. The economics here track the biology: the more dangerous reactivation becomes, the more value accrues to a test that identifies infection more reliably.
One Office Visit Changed How Clinicians Viewed the Test
Clinician feedback added a different kind of evidence. Health care providers responded positively to IGRA and viewed it as the preferred test for many patients, especially because the assay requires only a single visit. TST demands return attendance, and missed follow-up can be driven by transportation barriers, language barriers, childcare needs, and work schedules. A one-visit test does not solve every access problem, but it removes a structural obstacle that repeatedly undermines screening programs.
That operational advantage matters in TB control. A test that is accurate but difficult to complete will fail many of the people it is meant to reach. The convenience of IGRA may be especially relevant for contact investigations and for patients already navigating complex medical care, where extra visits can easily be lost in the churn of competing priorities.
Ontario’s Funding Decision Balances Better Targeting Against Upfront Spending
Ontario’s assessment lands on a careful but practical conclusion. IGRA has good diagnostic accuracy and is cost-effective or cost-saving in the populations where the Canadian TB Standards already favor its use. Public funding across all examined subgroups would raise total provincial spending by a modest amount in some pathways and by a substantially larger amount in others, but the population-level estimate is shaped by the mix of groups tested and the way the assay is deployed.
In eligible BCG-vaccinated immigrant populations and in BCG-vaccinated people identified during contact investigations, the case for IGRA is strongest because the assay avoids the false-positive burden associated with TST. In immunocompromised patients, the test may cost more up front because it identifies people who need further evaluation, yet that same feature can prevent missed infection in a population where reactivation carries greater clinical stakes. The assessment therefore supports a targeted strategy rather than a one-size-fits-all replacement of TST.
The remaining uncertainty is not about whether IGRA works, but how health systems should balance its higher immediate cost in some groups against the downstream consequences of missed or inaccurate screening. Ontario’s data suggest that the answer depends on who is being tested, how likely latent infection is to reactivate, and how much value the system assigns to a test that reduces repeat visits while improving diagnostic precision.