LTBI screening in tuberculosis low-incidence country – can a negative IGRA “cancel” a positive TST result?

<bold>Introduction:</bold> Tuberculin skin test (TST) and interferon gamma release assay (IGRA) are tests aimed to diagnose latent tuberculosis infection (LTBI) and predict the risk for active disease. Both tests have limitations, and none is superior. Whether a negative IGRA can be used to rule out positive TST test in low TB incidence countries is unknown. <bold>Methods:</bold> Retrospective study, with data from a single TB clinic in Israel. Data of all patients screened for LTBI with both TST and IGRA between 2012-2017 were extracted, including demographics, test indication, chest X ray, TST and IGRA results, follow-up length, and whether preventive TB treatment was given. Patients who had a positive TST and negative IGRA (and no TB) were included. The outcome was development of active TB during follow-up. Statistical analysis was done with the use of ‘rule of three’ technique for zero numerator results to calculate the upper CI of TB incidence. <bold>Results:</bold> We found 2311 patients with both TST and IGRA results, of whom 1023 were health care workers (HCW), and 1288 were candidates for immunosuppressive treatment. 754 HCW and 994 immunosuppressed patients had a positive TST, a negative IGRA test and did not receive TB preventive treatment. Median follow-up was 4.4 years. None of the patients developed active TB during follow up. The 95% confidence interval for the risk for active TB disease was 0.00-0.0039 for HCW and 0.00-0.0030 for immunocompromised patients. <bold>Conclusion:</bold> The risk of active TB disease in HCW and immunocompromised patients with a positive TST and a negative IGRA is extremely low in the setting of a low TB incidence country. This can be a basis for a better screening strategy for LTBI.