Disclosures: Ho reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
October 12, 2021
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Use of IGRAs can reduce overdiagnosis of latent TB infection, study says

Disclosures: Ho reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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The use of interferon gamma release assays can reduce overdiagnosis of latent tuberculosis infection among people from countries that use the bacille Calmette-Guérin vaccine and have moderate to high rates of disease, according to a study.

“The CDC’s Tuberculosis Epidemiologic Studies Consortium (TBESC) convened an expert panel of tuberculosis (TB) researchers and public health officials to review research gaps in the diagnosis and treatment of latent TB infection and recommend a research goal for the consortium,” CDC epidemiologist Christine Ho, MD, MPH, told Healio.

Christine Ho

“The panel concluded that large-scale assessment of the tuberculin skin test (TST) compared with interferon gamma release assays (IGRAs) would provide important information on how these tests perform in key populations in the U.S.,” HO said. “The results from this assessment could be used globally to improve treatment to prevent TB disease and help deliver better public health programs.”

Ho and colleagues performed an observational cohort study, enrolling participants with a high risk for latent TB infection or progression to TB disease at 10 U.S. sites with 18 affiliated clinics. According to the study, participants included close contacts of people with infectious TB, people born in countries whose populations in the U.S. have high (100 cases per 100,000 people) or moderate (10 to 99 cases per 100,000 people) TB incidence, and people with HIV. The researchers interviewed participants to collect demographics and medical risk factors, and they administered all three tests to each participant.

Overall, between July 12, 2012, and May 5, 2017, 21,846 participants were available for analysis, including 3,790 born in the U.S. and 18,023 born outside the U.S. According to the study, among non-U.S.-born participants, the risk ratio comparing the proportions of TST-positive results (43.2% of participants) to QuantiFERON-positive results (26.5% of participants) was 1.6 (95% CI, 1.6-1.7), whereas the risk ratio for the comparison with the proportion of T-SPOT.TB-positive results (21.6% of participants) was 2 (95% CI, 1.9-2.1).

Among U.S.-born participants, there was less variation in the proportions of positive results across all tests. The risk ratios for the proportion of TST-positive results (10.9% of participants) compared with the proportion of QuantiFERON-positive results (12% of participants) and T-SPOT.TB-positive results (8.1% of participants) were 0.9 (95% CI, 0.8–1) and 1.3 (95% CI, 1.2–1.6), respectively.

According to the study, 20,149 participants had results for all three tests. Researchers found that consistency between TST and IFN- release assay results varied by age among non-U.S.-born participants and was greatest among the 848 non-U.S.-born children aged younger than 5 years. They added that 204 of 234 non-U.S.-born children aged younger than 5 years with at least one positive test were TST-positive and IFN- release assay-negative, whereas the proportion of non-U.S.-born participants who were TST-negative but IFN- release assay-positive ranged from one of 199 children younger than 2 years to 86 of 594 participants aged 65 years and older.

“In countries with low rates of TB disease and similar epidemiology to the U.S., the use of IGRAs will reduce overdiagnosis of latent TB infection among people from countries with BCG vaccination and moderate to high rates of TB disease,” Ho said. “The study findings reinforce U.S. clinical practice recommendations to use IGRAs to diagnose TB infection among people at risk. This will allow clinicians and public health programs to effectively focus on those who would most benefit from treatment to prevent TB disease.