Can the Interferon-γ Release Assay Help Diagnose Active Tuberculosis in the Elderly?

Chi Chiu Leung and Wing Wai Yew Chest 2008;134;471 DOI 10.1378/chest.08-0448

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Can the Interferon- Release Assay Help Diagnose Active Tuberculosis in the Elderly?
To the Editor: We read with great interest the article by Kobashi et al1 on the clinical utility of QuantiFERON TB-2G (Cellestis Ltd; Carnegie, VIC, Australia) for elderly patients with active tuberculosis (TB). Despite a relatively limited sample size, the article confirmed that the sensitivity of QuantiFERON TB-2G was not significantly reduced among very old subjects with culture-confirmed TB as compared to younger subjects (77% vs 87%, p 0.185), in sharp contrast with the tuberculin skin test (TST). However, conflicting results have been reported regarding the clinical utility of the interferon- release assay (IGRA) in the diagnosis of active TB, depending on the methodology.1– 4 Very high sensitivity ( 90%) and specificity ( 95%) were similarly reported in a casecontrol study2 involving bacteriologically confirmed TB cases in a low-prevalence area. In two studies3,4 of patients with suspected disease, the negative predictive values for active TB were approximately 85%, but the positive predictive values were only 23% and 60%. The differing sensitivity of TST and T-SPOT.TB (Oxford Immunotec; Oxford, UK) for latent tuberculosis infection (LTBI) among elderly subjects has been reported in another study.5 Despite this, the clinical utility of IGRA in confirming the diagnosis of active TB depends critically on the prevalence of disease among subjects in the sample tested. In contrast with LTBI, untreated active TB carries high morbidity and mortality. Missing 15 of 100 patients with active TB is quite unacceptable. While the IGRA may be useful for establishing LTBI, it cannot accurately differentiate between infection and disease. Indeed, none of the existing LTBI tests can rule in or rule out active TB. Their roles may be further limited among the elderly with high background LTBI prevalence in most Asian countries.1–5 When bacteriologic confirmation is not available, the overall clinical picture must be taken into account in arriving at a diagnosis sensibly. Chi Chiu Leung, MB, FCCP Tuberculosis and Chest Service, Department of Health Wing Wai Yew, MB, FCCP Tuberculosis and Chest Unit, Grantham Hospital Hong Kong, China The authors have no conflicts of interest to disclose. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). Correspondence to: Chi Chiu Leung, MB, FCCP, Department of Health, 4/F Shaukiwan Jockey Club Clinic, 8 Chaiwan Rd, Shaukiwan, Hong Kong, China; e-mail: cc_leung@dh.gov.hk DOI: 10.1378/chest.08-0448

immunospot assay in the diagnosis of active pulmonary tuberculosis. Chest 2007; 132:959 –965 5 Leung CC, Yam WC, Yew WW, et al. Comparison of T-Spot.TB and tuberculin skin test among silicotic patients. Eur Respir J 2007; 31:266 –272

Clinical Utility of the InterferonRelease Assay for Elderly Patients With Active Tuberculosis
A Word of Caution
To the Editor: Kobashi et al1 recently reported on the sensitivity of the QuantiFERON TB-2G (QFT-2G) [Cellestis Ltd; Carnegie, VIC, Australia] interferon- release assay (IGRA) in 30 subjects aged 80 years with active tuberculosis (TB) [77%], with similar results than a previous study by Mori et al2 (n 10; sensitivity, 80%), thus confirming the higher sensitivity of QFT-2G vs tuberculin skin testing (TST) in this population. We disagree, however, with the conclusion that the IGRA can be used as a diagnostic method for TB in elderly patients. The IGRA and TST are markers of infection by Mycobacterium tuberculosis complex, but are not reliable markers of activity of the disease. Although interferon- levels do reflect to some extent disease activity, IGRAs should not be used in a clinical setting to distinguish TB from latent tuberculosis infection (LTBI) and are not recommended in this indication.3 The infection rate by M tuberculosis

References
1 Kobashi Y, Mouri K, Yagi S, et al. Clinical utility of the QuantiFERON TB-2G test for elderly patients with active tuberculosis. Chest 2008; 133:1196 –2002 2 Detjen AK, Keil T, Roll S, et al. Interferon- release assays improve the diagnosis of tuberculosis and nontuberculous mycobacterial disease in children in a country with a low incidence of tuberculosis. Clin Infect Dis 2007; 45:322–328 3 Dewan PK, Grinsdale J, Kawamura LM. Low sensitivity of a whole-blood interferon- release assay for detection of active tuberculosis. Clin Infect Dis 2007; 44:69 –73 4 Kang YA, Lee HW, Hwang SS, et al. Usefulness of wholeblood interferon- assay and interferon- enzyme-linked
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Figure 1. Relationship between pretest and posttest probability of disease with a test having a sensitivity of 77% and a specificity of 97% (ie, that of QFT-2G [Bayes theorem]).6 The upper curve yields posttest probability if the test result is positive and the lower curve if the test result is negative. Pretest probability depends on estimated prevalence of disease in the population studied. Doted arrows show a pretest probability of 80% (estimated prevalence of LTBI in subjects aged 80 years), and a posttest probability of LTBI or TB of 50% if the QFT-2G result is negative.
CHEST / 134 / 2 / AUGUST, 2008

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Can the Interferon-γ Release Assay Help Diagnose Active Tuberculosis in the Elderly? Chi Chiu Leung and Wing Wai Yew Chest 2008;134; 471 DOI 10.1378/chest.08-0448 This information is current as of March 11, 2010
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