Factors Associated with the Performance of a Blood-Based Interferon-γ Release Assay in Diagnosing Tuberculosis

Sally Banfield,David Burgner,Aris Siafarikas,Elaine Pascoe,Aesen Thambiran,Jean Louis Herrmann

doi:10.1371/journal.pone.0038556

Abstract

BackgroundIndeterminate results are a recognised limitation of interferon-γ release assays (IGRA) in the diagnosis of latent tuberculosis (TB) infection (LTBI) and TB disease, especially in children. We investigated whether age and common co-morbidities were associated with IGRA performance in an unselected cohort of resettled refugees.MethodsA retrospective cross-sectional study of refugees presenting for their post-resettlement health assessment during 2006 and 2007. Refugees were investigated for prevalent infectious diseases, including TB, and for common nutritional deficiencies and haematological abnormalities as part of standard clinical screening protocols. Tuberculosis screening was performed by IGRA; QuantiFERON-TB Gold in 2006 and QuantiFERON-TBGold In-Tube in 2007.ResultsComplete data were available on 1130 refugees, of whom 573 (51%) were children less than 17 years and 1041 (92%) were from sub-Saharan Africa. All individuals were HIV negative. A definitive IGRA result was obtained in 1004 (89%) refugees, 264 (26%) of which were positive; 256 (97%) had LTBI and 8 (3%) had TB disease. An indeterminate IGRA result was obtained in 126 (11%) refugees (all failed positive mitogen control). In multivariate analysis, younger age (linear OR = 0.93 [95% CI 0.91–0.95], P<0.001), iron deficiency anaemia (2.69 [1.51–4.80], P = 0.001), malaria infection (3.04 [1.51–6.09], P = 0.002), and helminth infection (2.26 [1.48–3.46], P<0.001), but not vitamin D deficiency or insufficiency, were associated with an indeterminate IGRA result.ConclusionsYounger age and a number of common co-morbidities are significantly and independently associated with indeterminate IGRA results in resettled predominantly African refugees.

Highlights

Mycobacterium tuberculosis (MTB) infects over one third of the global population and tuberculosis (TB) disease results in approximately 1.3 million deaths annually, largely in high incidence, resource-poor countries. [1] With increasing migration from high to low incidence regions, the majority of TB notifications in resource-rich countries such as Australia [2] and the UK [3] are in those born overseas
We investigated the effect of these co-morbidities on the performance of QFT and QFT-IT as a screening tool for TB infection in a large cohort of recently resettled unselected paediatric and adult refugees in Australia
Laboratory investigations included an immunochromatographic assay for Plasmodium falciparum (Binax NOWH, Portland, USA), single thick and thin blood films for malaria, serology for schistosomiasis and for strongyloidiasis (EIA), [21] automated full blood count and leucocyte differential, iron stores, total calcium, phosphate, alkaline phosphatase and 25-hydroxyvitamin D, all performed by standard laboratory assays

Summary

Introduction

Mycobacterium tuberculosis (MTB) infects over one third of the global population and tuberculosis (TB) disease results in approximately 1.3 million deaths annually, largely in high incidence, resource-poor countries. [1] With increasing migration from high to low incidence regions, the majority of TB notifications in resource-rich countries such as Australia [2] and the UK [3] are in those born overseas. Mycobacterium tuberculosis (MTB) infects over one third of the global population and tuberculosis (TB) disease results in approximately 1.3 million deaths annually, largely in high incidence, resource-poor countries. [1] With increasing migration from high to low incidence regions, the majority of TB notifications in resource-rich countries such as Australia [2] and the UK [3] are in those born overseas. [10] Interferon-c release assays (IGRA), which quantify the interferon (IFN)-c response of whole blood (QuantiFERONH-TB Gold, QFT and QuantiFERONH-TB Gold In-Tube, QFT-IT, Cellestis, Australia) or isolated mononuclear cells (T-Spot.TB, Immunotech, UK) to largely MTB-specific antigens, are increasingly used in resource-rich settings. Indeterminate results are a recognised limitation of interferon-c release assays (IGRA) in the diagnosis of latent tuberculosis (TB) infection (LTBI) and TB disease, especially in children. We investigated whether age and common comorbidities were associated with IGRA performance in an unselected cohort of resettled refugees

Methods

Results

Conclusion