Another day another dollar.

Recently published by the AJRCCM (American Journal of Respiratory and Critical Care Medicine) is this study from South Africa into the potential effects of a Mantoux (TST) on interferon-γ-release-assays (IGRAs)

The study group hypothesised that a prior TST could boost subsequent responses and evoke a ‘false positive’ boosted IGRA result. They noted that the tuberculin used, PPD RT-23, contains many antigens, including ESAT-6 and CFP-10. In their FAQ Cellestis advise that when stimulated with TB specific antigens ESAT-6 and CFP-10 T-cells respond by secreting IFN-y. The measurement of IFN-y is time sensitive and if it occurs less than 24 hours after stimulation only effector T-cells are measured (effector T-cells are the ones present at infection). Should the measurement be made at a time greater than 24 hours memory T-cells are also measured (memory T-cells contain a record of the immune response to past infections and require time to convert to effector T-cells). In this way the IGRAs can differentiate between actual infection and past infection.

It should be noted out that the original QuantiFERON (QFT-TB) used PPD but limited the time to less than 24 hours and it should be further noted that there may be an inherent time difference between in vivo (IGRA) and in situ (TST) testing methods.

However by observation the study group found that the potential for IGRA boosting occurred +3 days after the TST was placed and they therefore advised that

IGRAs should ideally be performed at no more than three days after a TST.

This could have serious implications for existing TB guidelines as the TST should be read between 48 and 72 hours after administration which leaves little time to use an IGRA to confirm a +TST.

UK-based National Institute for Clinical Excellence (NICE; (6)) and revised Canadian guidelines (7) recommend a two- step strategy (TST followed by an IGRA up to 6 weeks later in the UK guidelines) for the detection of LTBI. This recommendation is based on a cost-benefit analysis

This could be a problem for policy makers at institutions such as NICE who have already accepted the evidence that IGRA are superior to TST and are on notice to consider further evidence;

Interferon-gamma tests showed little evidence of being affected by prior BCG vaccination, and showed stronger correlation with exposure categories than did TST. This was shown in low prevalence groups, in household contacts, and in outbreak situations. The specificity of interferon-gamma tests seemed better, and there was less potential for false positive results...

...Evidence is emerging on the performance of interferon-gamma tests. If this new evidence is
significant, NICE will consider updating the guideline.

Decreasing the time between TST and IGRA from 6 weeks to maximum 24 hours is going to be a logistical problem making the IGRA only option more feasible and cost effective.