...the most likely explanation for the high rate of failed PHA mitogen control responses relates to the functionally immature immune system of infants and young children...This is where I dont quite see the logic. If IGRA has the ability to demonstrate that some immune systems are immature, a feature not present with skin testing, why is skin testing preferred? With an IGRA you know when the immune system is dysfunctional, with the TST it becomes just another false negative.
In addition to the high proportion of indeterminate assay results, significant discordance between the results of tuberculin skin testing and IGRA in children has been reported. Exploring the immunology underlying this discordance may help in the development of more accurate and reliable immunodiagnostic tests for the diagnosis of TB in children. In addition, long-term follow-up studies are needed to determine the true predictive value of IGRA for the development of active TB disease. We believe that until such data are available, IGRA should not be used as replacement tests for the tuberculin skin testing in children.
The discordance between IGRA and TST is well documented and there are numerous studies (like this) showing that the discordance is due to the failure of TST
The QFT assay was positive in all 21 of the children, and the Mantoux test was negative at first testing in 2 children (1 of whom was the sentinel case).and this
In conclusion, QFT can be a substitute for TST in detecting latent TB infection in childhood contacts aged less than or equal to 5 years, especially in those who may have a false-positive TST due to BCG vaccination or non-tuberculous mycobacterial infection.and this
IGRAs showed high diagnostic value in bacteriologically confirmed childhood TB. Their advantage in this study, when performed in addition to the TST, was the ability to distinguish -positive TST results caused by nontuberculous mycobacterial disease, thereby reducing overdiagnosis of TB and guiding clinical management.In the last study 54% of the children were less than 3 years old.
Connell calls for long-term follow-up studies to determine the true predictive value of IGRA - done!
Are IGRA indeterminates and discordance with TST sufficient reason to not use IGRAs on infants? No, says Dr Deborah A. Lewinsohn of Oregon Health Sciences University
despite the limitations, health care providers should embrace IGRA testing, rather than clinging to the "antiquated" TB skin test. She concludes,
"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."It's probably not relevant however Connell et al start their letter by saying
We read with interest the recent report by Haustein et al..The Haustein report came out in August 2009 so perhaps the Connell letter was a long time in limbo? It would appear that the more recent Connell letter is simply a rehash of points first raised in June 2008, things have moved on since then.
