Interferon Assays Useful in Latent TB Screening in Children

By David Douglas

January 02, 2020

NEW YORK (Reuters Health) - In children under age 15, interferon-gamma release assays (IGRAs) appear no less effective than the standard tuberculin skin test (TST) in detecting latent tuberculosis infection (LTBI) and offer high specificity and negative predictive values.

In an online paper in Pediatrics, Dr. Amina Ahmed of Levine Children's Hospital at Atrium Health, Charlotte, North Carolina, and colleagues note that reactivation of latent TB accounts for more than 80% of cases in the United States. Treatment can stop progression and is essential for elimination of the disease.

Children are a priority for screening, particularly children not born in the U.S., but the investigators say the optimal testing strategy is unclear. The TST has been used for more than a century but has limited specificity because of cross reactions to agents such as BCG vaccine.

IGRAs, available since 2000, do not have such limitations, but the researchers point out, "Questions remain, however, about which test is best for screening children, especially children not born in the United States in whom use of TST may result in overdiagnosis and overtreatment."

To investigate further, the researchers examined data on more than 3500 children (median age, 8.6 years), almost all of whom (92%) were born outside the U.S. They were tested with the TST and with two IGRAs: the QuantiFERON-TB Gold In-Tube test (QFT-GIT) and T-SPOT.TB test (T-SPOT).

To identify incident disease, the children were followed actively for two years, then with registry matches. Over a median of 4.3 years of follow-up, four children developed TB.

Sensitivities for progression to disease were low at 50% for both the TST and T-SPOT as well as for the QFT-GIT (75%), and confidence intervals were high. Corresponding specificities were 73.4%, 92.9%, and 90.1%.

"Although IGRAs performed no worse than the TST," say the investigators, "these low values are expected given known low rates of progression to tuberculosis disease and modification of progression by latent TB infection treatment."

Positive predictive values for TST, QFT-GIT, and T-SPOT were 0.2, 0.9 and 0.8. Corresponding negative predictive values (NPV) were 99.9. 100, and 100.

Summing up, Dr. Ahmed told Reuters Health by email, "The specificity of IGRAs was higher than for TST, with 70% fewer positive results compared with TST in non-U.S.-born children. This finding supports the observation that many non-U.S.-born children are likely over-diagnosed (and consequently overtreated) for LTBI. Most important for the clinician, the NPV of IGRAs was high. None of the 533 children with negative IGRAs and positive TSTs who were not treated for LTBI developed disease."

"In conclusion," she said, "the findings support the use of IGRAs to screen for LTBI in children of any age. It is important to note that no test is perfect, and clinical judgement needs to be used, especially among high-risk patients (e.g., young infants who are contacts to cases of TB). Among non-U.S.-born children who are targeted for LTBI screening, the use of IGRAs would substantially reduce overdiagnosis and overtreatment of LTBI, with improved use of resources."

SOURCE: and Pediatrics, online December 31, 2019.