Embracing IGRAs in children

In children primary tuberculosis disease is more common than reactivation disease. Due to immunologic immaturity, the incidence of TB following infection is higher in young children than in older children and adults. Children are immunologically mature by about 5 years of age, at which time the incidence of TB falls to adult rates and they begin to get adult type disease. When you look at the IGRA studies in children with active TB, and put the studies together, the numbers are still quite small. In seven reported studies looking at the sensitivity of the TST vs. QFT-G/GIT in active TB patients aged <18 years, the TST performs well in terms of sensitivity. The sensitivity of the IGRA in these combined studies is not as high, but the ranges in these seven studies are similar to what is seen in adults. There are less data for the T-SPOT.TB test, but in four available studies looking at children aged ≤19 years, T-SPOT performs quite well. Regarding specificity in children with the IGRA, a German study of 28 children with confirmed TB reported good sensitivity and specificity data for both tests. (Specificity was low for the TST in this study.) The other study on IGRAs in children was a Korean study in BCG-vaccinated children where 62 children aged 2 months to 14 years of age were tested; none of them had a known risk for TB and none were QFT-positive. There are still limitations in our knowledge of using IGRAs in children, with a paucity of data in children aged <5 years, increased frequency of indeterminate assays in children <5 years, and lack of longitudinal data. Another issue is the required blood volumes for performing the IGRAs. Very few IGRA studies in children record failed phlebotomy, but some of those that do report high failure rates. What about QFT vs. T-SPOT? QFT is set up for specificity and that is good for addressing BCG. Clinicians should consider using both tests in children. There are more positive tests with T-SPOT than QFT-GIT in some studies, which may reflect increased sensitivity of T-SPOT compared to QFT-GIT. In children aged ≥5 years, IGRAs may be used in place of TST and are preferred to TST in some circumstances, including BCG-vaccinated children. TSTs are preferred to the IGRA in children aged <5 years. Both the IGRA and the TST should be considered, and one should take either positive as evidence of infection, particularly for TB suspects, HIV infection, and when children have an increased risk of progression of LTBI. Future research on IGRAs in children should address data on young high-risk children in low-incidence settings, longitudinal data in young children to inform 'window prophylaxis,' data on young immunosuppressed HIV-infected children, and more data on commercial tests with reduced blood volume requirements.