Rapid diagnosis of active pulmonary tuberculosis in the elderly using Enzyme-Linked immunospot assay for interferon-gamma
Journal
Journal of the American Geriatrics Society
Journal Volume
57
Journal Issue
12
Pages
2361-2362
Date Issued
2009
Author(s)
Abstract
To the Editor: Despite global control efforts, tuberculosis (TB) remains a serious threat to elderly people.1 The presentations of TB in older patients are different from in younger patients, and lower awareness of the disease in elderly people often results in a delay of diagnosis.2,3 Recently, an enzyme-linked immunospot (ELISPOT; T SPOT-TB; Oxford Immunotec Ltd, Oxford, UK) assay was developed to detect interferon-gamma produced by activated T cells after exposure to specific antigens of Mycobacterium tuberculosis (the early secretory antigenic target 6 and culture filtrate protein 10), but information regarding the usefulness of this assay for diagnosis of active TB in elderly patients is limited. Therefore, this study was performed to evaluate the performance of the ELISPOT assay for diagnosis of active pulmonary TB in elderly patients. The study was conducted in a 2,500-bed university-affiliated hospital in Taiwan after approval by the institutional review board of the hospital. All patients aged 65 and older with suspected pulmonary TB were prospectively enrolled from March 2007 to February 2009. Subjects were categorized as having confirmed TB if M. tuberculosis was recovered from sputum and bronchioalveolar lavage fluid, probable TB if a histological diagnosis (granulomatous inflammation and caseous necrosis) of a biopsied specimen was made or symptoms and signs of active TB were present in a patient who responded clinically to a full course of anti-TB treatment, and no TB if another diagnosis was made or clinical improvement was noted without anti-TB therapy. The ELISPOT assay was performed as previous described.4,5 Comparisons between groups were analyzed using chi-square and Fisher exact tests for categorical variables and the Student t-test for continuous variables. One hundred forty-seven patients were enrolled, with a mean age of 76.0 ± 7.1, and 67.3% were male. Eighty-three (56.5%) had a positive acid-fast smear, and 87 (59.2%) had positive ELISPOT results. There were 66 (44.9%) with confirmed TB, 13 (8.8%) with probable TB, and 68 patients (46.3%) with no TB. Fourteen of the 79 patients (17.7%) with active TB had extrapulmonary involvement. The overall sensitivity, specificity, positive predictive value, and negative predictive value for ELISPOT in diagnosis of active TB (confirmed and probable TB) were 82.3%, 67.6%, 74.7%, and 76.7%, respectively. The comparisons between the two groups (65–79 vs ≥80) are summarized in Table 1. The ELISPOT assay showed significantly higher sensitivity in patients younger than 80 (83.9%) than in those aged 80 and older (78.3%) (P=.046). This is the first study to evaluate the performance of ELISPOT assays in elderly patients with suspected active pulmonary TB. The overall sensitivity of ELISPOT assay for diagnosing active pulmonary TB in 147 elderly patients was 82.3%, suggesting that the ELISPOT assay may be a useful supplementary tool for assessment of elderly patients with suspected active pulmonary TB. Aging has been concerned to be one of the important factors that might affect the performance of the ELISPOT assay. This study demonstrated that the sensitivity of the ELISPOT assay was significantly lower in patients aged 80 and older (78.5%) than in those aged 65 to 69 (83.9%, P=.046). The sensitivity of the QuantiFERON TB-2G (QFT-2G) test (Cellestis Ltd, Carnegie, Australia), another test that measures interferon-gamma for the diagnosis of TB, was also noted to be significantly lower in patients aged 80 and older than in younger patients in a prospective study,6 although whether the decrease in the sensitivity of the ELISPOT assay and the QFT-2G test in elderly patients was a result of the aging process, which reduces the production of interferon-gamma induced by the two specific antigens, warrants further investigation. Ninety-eight patients in the current study also had QFT-2G test results, with 48 (49%) having positive results. The overall sensitivity, specificity, positive predictive value, and negative predictive value for QFT-2G test in the diagnosis of active TB were 68.5%, 75.0%, 77.1%, and 66.0%, respectively. The overall sensitivity of the QFT-2G test (68.5%) was lower than that of the ELISPOT assay (82.3%) although not statistically significantly different (P=.06). In addition to pulmonary TB, previous studies7–9 have shown that the ELISPOT assay was a useful adjunct test for diagnosis of extrapulmonary TB. In the current study, of the nine patients with disseminated TB, eight (88.9%) had positive ELISPOT assays, although whether the ELISPOT assay has a higher sensitivity for the diagnosis of disseminated TB in this age group requires further confirmation from large-scale studies. In conclusion, the ELISPOT assay could be a useful supplementary tool for the diagnosis of pulmonary TB in elderly patients, but its performance may decrease with aging. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Funding Disclosure: Funded by the Institute for Biotechnology and Medicine Industry (DOH97-DC-1501). Author Contributions: Study concept and design: Tan, Lai, Hsueh. Acquisition of data: Lai, Liao, Chou, Hsu, Huang. Analysis and interpretation of data: Tan, Lai, Hsueh. Preparation of manuscript: Tan, Lai, Hsueh. Sponsor's Role: The sponsor had no role in the design, methods, subject recruitment, data collection, analysis, of preparation of this letter.
SDGs
Other Subjects
bacterial antigen; gamma interferon; aged; aging; clinical assessment; enzyme linked immunospot assay; female; human; letter; lung lavage; lung tuberculosis; major clinical study; male; Mycobacterium tuberculosis; prediction; prospective study; sensitivity and specificity; T lymphocyte activation; Aged; Aged, 80 and over; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interferon-gamma; Male; Prospective Studies; Time Factors; Tuberculosis, Pulmonary
Type
letter