Oregon Health Sciences University
In reading over the following two studies I was reminded again over the dilemma that exists for some medical people and their contribution to the continuance of that dilemma. Two particular studies, Interferon Gamma Release Assays in the Evaluation of Children With Possible Mycobacterium tuberculosis Infection and Embracing Interferon-y Release Assays for Diagnosis of Latent Tuberculosis Infection are published in the latest edition of the Pediatric Diseases Journal and concern themselves with the finding of the study (yet to be published) by Hausein et al "The likelihood of an indeterminate test result from a whole-blood interferon-y release assay for the diagnosis of Mycobacterium tuberculosis infection in children correlates with age and immune status"
Of the study *Dr Deborah A. Lewinsohn says
This well-performed study represents the largest study of IGRA test performance in this vulnerable population to date. It provides just the sort of informative data needed to direct clinical use of IGRAs in pediatric populations. However, the main message is sobering. In this group of 237 children cared for at a tertiary care medical center, the QFT-IT assay was indeterminate in 83 children, a full 35% of the total study population. Moreover, an indeterminate result was associated with young age and immunocompromising conditions. As stated by the authors, an indeterminate result equates with an uninformative result. Hence, the test was most often uninformative in the children at high risk for developing TB after infection. Despite this finding, these results, as well as the growing body of literature regarding IGRAs in young children, support increasing use of IGRAs in children.In his reply **Dr Dwight A. Powell says
Although I agree with many of Dr. Lewinsohn’s comments, I think there are several areas in need of additional research before a universal acceptance of the use of IGRAs for children. These areHe concludes by saying
(1) explaining the high incidence of indeterminate results in young children assessed with whole blood IGRAs;
(2) assessing the risk of progression to TB disease in children with possible latent tuberculosis infection (LTBI) based on high tuberculin skin test (TST) reactions (> 15 mm induration) but negative IGRAs; and
(3) better defining the role of IGRAs as a reliable marker of TB disease in children.
What would be my approach to diagnosing TB in children? Until more data are available, I feel comfortable using an IGRA assay to screen children older than 4 years for LTBI who have had known contact with an adult case of TB disease within the past year.As I see it Powell expresses reluctance in using a diagnostic on children under 4 due to a lack of the same research that he is reluctant to provide. By using the diagnostic (and it has been universally proven and accepted as being more accurate) experience can be gained and as we all know, wisdom does not come before experience.
Dr Lewinson leads the way;
In summary, it is time for child health providers to embrace IGRAs rather than to cling to the antiquated TST. Expanded use of IGRAs in children, both through well-designed clinical research studies and reports of clinical practice would serve to promote better health care for children. As noted above, dual testing with IGRA’s and TST can be used in high risk young and/or immunocompromised children to increase sensitivity of diagnosed LTBI. Additionally, IGRA’s may be useful as a more specific test than TST in low risk BCG-vaccinated children. Recommendations for use of IGRAs in young children are curtailed not by negative data, but rather by lack of sufficient data in young children to support such guidelines. Cumulative clinical data can inform these guidelines. Moreover, cumulative clinical experience will clarify the deficiencies of the currently available IGRAs and proactively push manufacturers to improve the performance of their test(s) in young children. If child health providers reject IGRA use in young children, how can we expect continued improvements? There is no doubt that critical research gaps and test performance deficiencies remain, preventing the replacement of TST with IGRAs in young children at the current time. Especially, regarding QFT-IT, better test performance in young children and decreased blood volume requirements are needed. IGRAs need to be studied in a large household study of young contacts of adults with infectious TB conducted in the United States/Europe. But these issues need not immobilize us. We need to keep moving forward to prevent child health from falling behind, gain more experience with IGRAs to create rational guidelines, and continue to demand attention to one of the most vulnerable populations to TB.
*(from the Division of Infectious Diseases, Department of Pediatrics, Oregon Health Sciences University, Portland, Oregon)
**(from both the Department of Pediatrics, The Ohio State University College of Medicine and Section of Infectious Diseases, Nationwide Children’s Hospital, Columbus, OH)






