Another "expert opinion"

In the blog Australian Tuberculosis Review (edited by Dr John Thompson Canberra, Professor Adrian Sleigh Australian National University and Associate Professor Paul Kelly Australian National University) the study Discordant QuantiFERON-TB Gold test results among US health care workers with increased risk of latent tuberculosis infection: a problem or a solution? was published with the following comment;

There has never been a universal gold standard for LTBI using the TST and the same goes for QFT-G et al. Each region has to find its own cut off point.
JT

JT (who I presume is Dr John Thompson) has been consistent with this meme; the cutoff points for QFT should make allowance for differing populations and circumstances as does the TST.

As has been pointed out before, there is no single international ‘cutpoint’ for such tests when it comes to diagnosing latent tuberculous infection. Each country or region must determine its own values.

JT

This argument appears to be flawed; whilst noting that there is no gold standard all tests for LTBI must conform to the standard of TST. What JT et al fail to acknowledge is that the TST and the QFT share little scientific "common ground", the TST uses a PPD

purified protein fraction is isolated from culture media filtrates of a human strain of Mycobacterium tuberculosis

which is injected into the patient whereas the QFT utilises antigens specific to Mycobacterium tuberculosis to stimulate whole blood extracted from the patient.

The only real commonground is that both tests are for determining exposure to TB.

The US FDA list three 'cutpoint’ for TST; ≥ 5 mm, ≥ 10 mm and ≥ 15 mm of induration whereas the approval for Quantiferon Gold lists no such 'cutpoint'. In their guidelines the US CDC accept the cut off points determined by the manufacturer and in discussing the features and performance of the tests and note that

less agreement between TST and QFT-G results is predictable because fewer and more specific antigens are used in QFT-G. QFT-G is not affected by prior BCG vaccination (1) and is expected to be less influenced by previous infection with nontuberculous mycobacteria (5). TSTs are variably affected by these factors. QFT-G does not trigger an anamnestic response (i.e., boosting) because it does not expose persons to antigen. Injection of PPD for the TST can boost subsequent TST responses, primarily in persons who have been infected with NTM or vaccinated with BCG. Compared with the TST, QFT-G might be less affected by boosting from a previous TST.

In particular they state that the antigens used in Quantiferon Gold

impart greater specificity than is possible with tests using purified protein derivative as the tuberculosis (TB) antigen

JT is correct in that cutoff points for tests using tuberculin need to be adjusted to the circumstances but offers no evidence as to why Quantiferon should also be adjusted. The Pollock study that JT refers to is also in some error in that they incubated the QFT sample past the recommended time

Extended assays using the antigens ESAT-6 and CFP-10 confirmed the positive results detected by the overnight assays and yielded positive results for an additional 7/36 19%) of individuals; strikingly , all 36 HCWs had strongly positive test results with assays using purified protein derivative.

Activating memory T cells is unnecessary and confounds the diagnosis as, unlike the TST, Quantiferon is able to differentiate between effector and memory T cells. Pollock acknowledge this

it is possible that the QFT-G assay identifies those at higher reactivation risk rather than all previously infected

and later studies have confirmed this

Results suggest QFT screening determines more accurately than TST the presence of LTBI with at least equivalent sensitivity for predicting progression to TB. The high rate of progression to active TB of
those QFT positive (14.6%), far greater than the 2.3% found for those TST positive, has significant health and economic implications for enhanced TB control.

It is disappointing that the Australian Tuberculosis Review has not reviewed all studies on TB (like this and this) and continues to offer a biased opinion unsupported by scientific fact.

Because most HCWs worldwide have been vaccinated with BCG, the QFT-G offers a significant improvement over the TST in tuberculosis screening programs and minimizes unwarranted use of tuberculosis prophylaxis.

Harada N, Nakajima Y, Higuchi K, Sekiya Y, Rothel J, Mori T.

The data indicate that the IGRA should replace the TST in serial testing of HCW in high income, low incidence countries. The recommendations to use the IGRA in order to verify a positive TST only should be reconsidered

A. Nienhaus, A. Schablon, C. Le Bâcle, B. Siano and R. Diel