Another box ticked

With regards to literature on QuantiFERON we often read informed opinions that are generally positive with the caveat "further studies are needed", in particular regarding clinical accuracy;

additional studies are needed to understand the reproducibility and relative accuracy of the test before its utility in prospective screening programs can be defined.

Well this lot from Finland did just that

New interferon gamma release assays (IGRAs) to detect an exposure to Mycobacterium tuberculosis have been recently launched. The majority of the studies in temperate climate countries agree that these methods have superior specificity and equal or even superior sensitivity over Tuberculin Skin Tests (TSTs) in the detection of latent tuberculosis infection (LTBI). However, reproducibility data of IGRAs are virtually missing.

They found that considering the multiple steps of the method, inter lot variability and biological variation the performance of IGRA was

well in accordance with the reported imprecision for other manual immunodiagnostic tests

The implication of this analysis is that reports of IGRA anomalies indicate a failure of the laboratory to observe

strict adherence to the standard operation procedure

Some labs took this on board

The tracking of indeterminate results is suggested as an important quality control measure.

whilst others shot the messenger

Of particular concern in our study was the relatively high “failure” rate of the whole blood IFN-γ assay...The 17% failure rate in our study therefore represents the “real world” use of this assay in paediatric clinical practice. 

These findings were disputed

Connell et al uses the QuantiFERON‐TB Gold (QFT‐Gold) test for tuberculosis (TB) infection, but it contains methodological inaccuracies. Unfortunately, the interpretation of the test by Connell et al was not that recommended by the manufacturer. The authors arbitrarily introduced a restriction on the nil control of the QFT‐Gold test to < 1 IU/ml interferon (IFN)‐γ, falsely generating a number of “failed” tests. As a result, the data presented by Connell et al significantly overestimate the number of invalid test results and may be misleading to readers.

Not all paediatricians Connell's problem with indeterminates

Of the 207 children included in the analysis, 3 children (1.4%) had indeterminate results, all because of a mitogen response that was below the allowable cutoff value.

As the Lighter study point out, there are other serious "real world" problems with persisting with the TST;

If the QFT were to be used as the diagnostic test for LTBI in children and treatment decisions were based on its results alone, as is the case now for adults and is also the practice for children in some health departments, including that in New York City, many fewer children would require isoniazid prophylaxis. On the basis of the results of this study, up to three fourths of children with positive TST results would not have been treated.

Clearly, the public health implications of switching from the TST to the QFT for the management of LTBI in children are significant