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

Abstract

Background Indeterminate 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. Methods A 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. Results Complete 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. Conclusions Younger age and a number of common co-morbidities are significantly and independently associated with indeterminate IGRA results in resettled predominantly African refugees.

Extremes of Age Are Associated with Indeterminate QuantiFERON-TB Gold Assay Results

“…The clear majority of indeterminate results occurred due to insufficient interferon gamma production in response to stimulation with PHA, which is consistent with data from other studies (10)(11)(12). Our results show that there is a significant relationship between age and PHA-induced interferon gamma responses, with an increasing trend in the first few years of life and a decreasing trend during adult life, likely reflecting immune maturation and subsequent immunosenescence.…”

“…Previous publications, including our own, have shown that indeterminate QFT-GIT results occur in a considerable proportion of children evaluated for TB infection (5,9,10). However, few publications have specifically focused on indeterminate results in adults, and even fewer have included a comparison of the performance of QFT-GIT assays between pediatric and adult patients (11,12).…”

Performance of Interferon-Gamma and IP-10 Release Assays for Diagnosing Latent Tuberculosis Infections in Patients with Concurrent Malaria in Tanzania

“…10 Although we found decreased IFN-γ responsiveness to mitogen stimulation during acute malaria infections, the majority of the malaria patients responded well above the cutoff for positive mitogen response, and we were unable to demonstrate a direct effect on the QFT test. However, we did find an increased IP-10 indeterminate rate.…”

“…1 A series of immunosuppressive conditions are known to compromise the IGRA test performance including human immunodeficiency virus (HIV) infection and low CD4 cell count, [2][3][4][5] glucocorticoid treatment, 6 cigarette smoking, 7 severe disease in children, 8 and helminth infection. 9,10 So far, no systematic evaluation of the possible effect of malaria infection on IGRA test performance has been done.…”

Level of Exposure of Childhood Tuberculosis with Adult Pulmonary Tuberculosis Household Contacts

“…(MTB) could be used to diagnose the absence of TB infection in the body. 18 The immune system of children can be measured by the intake status related to the nutrition status of children. Even though the relevance of chronic disease exposure such as pulmonary TB that had directly affects children's nutrition status, predicting it as the measuring association is still difficult.…”