Seasonal variation in the performance of QuantiFERON-TB Gold In-Tube assays used for the diagnosis of tuberculosis infection
Introduction
Interferon-gamma release assays (IGRAs) detect interferon-gamma responses following in vitro stimulation of blood with mycobacterial antigens [1], and are used widely throughout the U.S. and Europe for the detection of tuberculosis (TB) infection [2]. Of the two commercially available IGRAs, QuantiFERON-TB Gold assays are more commonly used in routine clinical practice than T-SPOT.TB assays [2].
IGRAs have several limitations including significant proportions of indeterminate assay results in certain patient populations and suboptimal sensitivity in patients with active TB [[3], [4], [5]]. Additionally, numerous studies indicate that IGRAs are not particularly robust, with minor variations in sampled blood volumes, intensity of assay tube shaking and delays in sample incubation having considerable impact on interferon-gamma responses and consequently assay results [3].
Data from a recent ex vivo study suggest that the performance of IGRAs is also influenced by environmental temperatures to which assay tubes are exposed prior to incubation [6]. As ambient temperature is not usually controlled during sample transport in routine clinical settings, we hypothesized that IGRA performance may vary between seasons in temperate climates. This study aimed to determine whether there is seasonal variation in the performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) assays.
Section snippets
Materials
We retrospectively studied data from QFT-GIT assays (Cellestis/Qiagen, Carnegie, Australia) processed routinely at a large independent, accredited diagnostic service provider in London between December 2009 and May 2014. The QFT-GIT samples originated from external healthcare providers or from the in-house phlebotomy services. Samples from the former are transported to the laboratory by car or motorcycle without temperature monitoring. All samples were incubated within 16 h, as per
Results
A total of 31932 QFT-GIT assays were included in the analyses. Of these, 8044 were performed in spring (March–May), 7376 in summer (June–August), 8996 in autumn (September–November), and 7516 in winter (December–February).
Discussion
To our knowledge, this is the first study to show significant seasonal variation in the performance of QFT-GIT assays, and it is one of the largest studies investigating IGRAs to date.
We found that positive QFT-GIT results were significantly more common in spring and summer. Furthermore, the proportion of indeterminate results was significantly higher in autumn. This finding is consistent with a Swiss study that analysed 1429 T-SPOT.TB assays (which being ELISPOT-based assays differ from
Conflicts of interest
MT received QuantiFERON-TB Gold assays at reduced cost for another research project from the manufacturer (Cellestis/Qiagen). The manufacturer had no influence on the study design, data interpretation, writing of the manuscript or decision to submit the data for publication.
Funding
MT was supported by a Clinical Lectureship provided by the U.K. National Institute for Health Research. MT and SMJ were additionally supported by funding provided by the Technology Strategy Board/Innovate U.K. [29617-210153].
Contributors
Study concept: MT and SM-J. Data analyses: MT, NC, VC, PE and SM-J. Data interpretation: MT, NC, VC, CF-T, NK, KF, SM, PE and SM-J. Drafting of the manuscript: MT, NC, PE and SM-J. All authors critically read, commented on, and approved the final version of the manuscript.
Ethical considerations
Under current U.K. health research ethics regulations, research limited to secondary use of information previously collected in the course of normal care without intention to use it for research does not require research ethics committee review, if patients or service users are not identifiable to the research team.
Acknowledgements
The authors thank the Met Office National Meteorological Archive for kindly providing temperature data for St. James's Park, London.
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