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Original Research: TUBERCULOSIS |

Clinical Utility of the QuantiFERON TB-2G Test for Elderly Patients With Active Tuberculosis* FREE TO VIEW

Yoshihiro Kobashi, MD, PhD; Keiji Mouri, MD; Shinich Yagi, MD; Yasushi Obase, MD, PhD; Naoyuki Miyashita, MD, PhD; Niro Okimoto, MD, PhD; Toshiharu Matsushima, MD, PhD; Takeshi Kageoka, MD, PhD; Mikio Oka, MD, PhD
Author and Funding Information

*From the Division of Respiratory Diseases (Drs. Kobashi, Mouri, Yagi, Obase, Miyashita, and Oka), Department of Medicine, Kawasaki Medical School, Kurashiki, Japan; the Division of Respiratory Diseases (Dr. Okimoto), Department of Medicine, Kawasaki Medical School Kawasaki Hospital, Okayama, Japan; the Division of Respiratory Diseases (Dr. Matsushima), Kurashiki Daiichi Hospital, Oimatsuchou, Kurashiki, Japan; and the Department of Laboratory Division, Kurashiki Central Hospital, Kurashiki, Japan.

Correspondence to: Yoshihiro Kobashi, Division of Respiratory Diseases, Department of Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan; e-mail: yoshihiro@med.kawasaki-m.ac.jp



Chest. 2008;133(5):1196-1202. doi:10.1378/chest.07-1995
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Objective: To evaluate the response to the QuantiFERON-TB-2 Gold (QFT-2G) test (Cellestis Ltd; Carnegie, VIC, Australia) in elderly patients with active tuberculosis (TB) to determine whether the QFT-2G test might be a feasible method for diagnosing TB infection in this group of patients.

Methods: The subjects were 30 elderly patients with active TB and 100 younger patients with active TB. The QFT-2G test results were analyzed in relation to combined and separate responses to early secretory antigenic target 6-kD (ESAT-6) protein and culture filtrate protein 10 (CFP-10) antigens.

Results: Of the 30 elderly patients with active TB, 27% had a positive tuberculin skin test (TST) result and 77% had a positive QFT-2G test result. Of the 100 younger patients with active TB, 70% had a positive TST result and 87% had a positive QFT-2G test result. Although there was no significant difference between the two patient groups in the positive rate for the QFT-2G test results (p = 0.185), there was a significant difference in the rates of positive TST results between the elderly and younger patients (p = 0.012). The positive test result rate for both ESAT-6 and CFP-10 antigens in the elderly patients (17%) was significantly lower than that in younger patients (37%; p = 0.038). There was an indeterminate result for the QFT-2G test in five elderly patients, and this might have been related to the presence of lymphocytopenia due to underlying disease. A negative result on the QFT-2G test was detected in two elderly patients, and this might have been related to the severity of the active TB.

Conclusion: We confirmed that the QFT-2G test might be a more useful method of diagnosing TB infection than the TST for elderly patients if peripheral lymphocyte counts have been preserved.

Although the tuberculin skin test (TST) has frequently been performed as the standard immunologic diagnostic tool for diagnosing tuberculosis (TB) infection in the 20th century, it does not reliably distinguish TB resulting either from previous immunization with the bacillus Calmette-Guerin (BCG) vaccine or from most nontuberculous mycobacteria.1

To replace the TST test, the availability of Mycobacterium tuberculosis (MTB) antigen-specific interferon (IFN)-γ release assays has represented a significant advance in the field of TB diagnosis.24 These assays measure T-cell-induced IFN-γ responses in MTB-specific peptides derived from the early secretory antigenic target 6-kD (ESAT-6) protein and culture filtrate protein 10 (CFP-10). These antigens are encoded by the genetic region of difference 1 that is present in all strains of MTB but is absent in nontuberculous mycobacteria and all BCG vaccine strains. The following two commercial IFN-γ assays have become available in the last few years: the QuantiFERON-TB-2 Gold (QFT-2G) assay (Cellestis Ltd; Carnegie, VIC, Australia) with an enzyme-linked immunosorbent assay used to measure IFN-γ concentrations in supernatants; and T-SPOT.TB (Oxford Immunotec; Oxon, UK) with an enzyme-linked immunospot assay used to detect individual T cells producing IFN-γ.56 The US Food and Drug Administration has approved the QFT-2G test and is currently evaluating the T-SPOT.TB test, which has been approved for use in Europe. These tests demonstrate a positive result for most persons with active TB disease. Of these tests, although the QFT-2G test was first used commercially in Japan in April 2005 for the diagnosis of TB, the T-SPOT.TB test has not yet been approved in Japan. Therefore, we performed the QFT-2G test for elderly patients with active TB and compared findings with those of the TST test in this study.

To date, although there have been many reports710 about the clinical usefulness of the QFT-2G test for patients with TB infection or latent TB infection, it has been indicated that care is needed when diagnosing TB infection for young pediatric patients (ie, those < 5 years old) or elderly patients. However, there have been few studies performing a detailed investigation of the clinical effectiveness for elderly patients (ie, those ≥ 80 years old) with active TB. Therefore, we evaluated the QFT-2G test responses in elderly patients with active TB to determine whether the QFT-2G test might be a feasible method for diagnosing TB infection in elderly patients (ie, those ≥ 80 years old) compared to that in younger patients (ie, those < 80 years old) according to the combined and separate responses to ESAT-6 and CFP-10 antigens.

Study Population

One hundred thirty patients including 30 elderly patients with active TB that had been confirmed by positive results of cultures of sputum, BAL fluid, pleural fluid, peritoneal fluid, or lymph node tissue samples were prospectively enrolled between April 2005 and June 2007. This study was approved by the ethics committee of each institution. The patients with active TB received their diagnoses at Kawasaki Medical School Hospital (1,072 beds), Kawasaki Medical School Kawasaki Hospital (650 beds), Kurashiki Central Hospital (1,570 beds), Kurashiki Daiichi Hospital (192 beds), or Asahigaoka Hospital (90 beds). We obtained written, informed consent from all patients in this study. All patients had either negative responses to serological tests for HIV or had no obvious risk factors for HIV infection. Subjects were divided into the following two groups: group 1 consisted of 30 elderly patients (≥ 80 years old) with active TB; and group 2 consisted of the remaining 100 younger patients (< 80 years old) with active TB. From patients in both groups with active TB, we collected demographic data regarding (1) any history of previous TB infection or antituberculous treatment, (2) other underlying diseases (ie, respiratory diseases such as healed pulmonary TB or COPD, and nonrespiratory diseases such as malignant disease, including leukemia, diabetes mellitus, renal failure with hemodialysis, collagen vascular disease, neurologic disease, GI disease, cardiovascular disease, and HIV infection), and (3) the receipt of immunosuppressive drugs within 3 months before enrollment into this study. Information regarding any previous Mantoux TST results and BCG vaccination inoculation, as well as information about laboratory findings (ie, WBC count, lymphocyte count, total protein concentration, and albumin concentration) and radiologic findings (ie, portion, extension, and cavity) were collected at the time of enrollment. Sputum or other appropriate respiratory samples were collected from all patients, and culture samples were obtained for the detection of mycobacteria.

Sample Collection and TST

Each patient in both groups had a heparinized blood sample collected by venipuncture for performing a whole-blood IFN-γ assay. Blood samples were collected before the administration of the Mantoux TST. For the TST test, 0.1 mL of tuberculin purified protein derivative (Nippon BCG Manufacturing; Tokyo, Japan [equivalent to three tuberculin units of purified protein derivative solution]) was injected intradermally into the volar aspect of the forearm, and the transverse induration diameter was measured 48 h later. The results of the test were interpreted by hospital staff based on the patient’s degree of risk, according to current guidelines11; a lower cutoff of 5 mm for a positive test result was used for each patient.

QFT-2G Test

The QFT-2G test was performed according to the recommendations of the manufacturer, and the test result was judged according to the guidelines of the Centers for Disease Control and Prevention.5 In brief, the test consisted of a negative control (a nil well [ie, whole blood without antigens or mitogen]), a positive control (a mitogen well [ie, whole blood stimulated with the mitogen phytohemagglutinin]), and two sample wells (ie, whole blood stimulated with either ESAT-6 or CFP-10). Whole-blood specimens were incubated for 18 h (overnight) at 37°C in a humidified atmosphere. The IFN-γ level of the nil well was considered to be the background value and subtracted from the values for the mitogen well and the antigen-stimulated wells. The test result was considered to be positive if the IFN-γ level in the sample well after stimulation with ESAT-6, and after the CFP-10 concentration was ≥ 0.35 IU/mL (after subtraction of the value for the nil well), irrespective of the result for the positive control well. The test was considered to be negative if the IFN-γ level was < 0.35 IU/mL and the IFN-γ level of the positive control well was ≥ 0.5 IU/mL. The test result was considered to be indeterminate if the IFN-γ level was < 0.35 IU/mL in both antigen wells and < 0.5 IU/mL in the positive control well.

Statistical Analysis

Information from the questionnaires, TST results, and whole-blood IFN-γ assay results were entered into spread sheet software (Excel 2000; Microsoft; Redmond, WA) and then were transferred to a statistical software package (Stata, version 7.0 Stata Corp; College Station, TX) for statistical analysis. The Pearson χ2 test was used to compare proportions in the two groups, and the McNemar test was used to compare paired proportions. The Mann-Whitney U test was used to compare unpaired results, and the Wilcoxon signed rank test was used to compare paired observations. Significance was recognized at p < 0.05.

Thirty elderly patients (ie, those ≥ 80 years old) with active TB (group 1) and 100 younger patients (ie, those < 80 years old) with active TB (group 2) were enrolled into this study between April 2005 and June 2007. The clinical diagnosis of the group 1 patients was pulmonary TB in 22 patients (including pulmonary tuberculoma in 2 patients), tuberculous pleuritis in 4 patients, miliary TB in 2 patients, tuberculous lymphadenitis in 1 patient, and pulmonary TB plus tuberculous pleuritis in 1 patient. The clinical diagnosis of the patients in group 2 was pulmonary TB in 59 patients (including pulmonary tuberculoma in 8 patients), tuberculous pleuritis in 14 patients, tuberculous lymphadenitis in 12 patients, pulmonary TB and tuberculous pleuritis in 8 patients, miliary TB in 5 patients, and tuberculous peritonitis in 2 patients. There was no significant difference in the clinical diagnoses between the two groups. Thirty patients in group 1 were confirmed as being positive for MTB by cultures of samples of sputum (13 patients with pulmonary TB and 1 patient with pulmonary tuberculoma), BAL fluid (7 patients with pulmonary TB, 2 patients with miliary TB, and 1 patient with pulmonary tuberculoma), pleural fluid (4 patients with tuberculous pleuritis and 1 patient with pulmonary TB and tuberculous pleuritis), resected lymph node (1 patient with cervical tuberculous lymphadenitis). Acid-fast smear results for sputum, bone marrow, BAL fluid, pleural or peritoneal fluid, or lymph node samples were positive in 14 of 30 patients (47%) in group 1. The remaining 16 patients had negative results for acid-fast smear and positive results for cultures for TB. One hundred patients in group 2 were confirmed as being positive for MTB by cultures of samples of sputum (32 patients with pulmonary TB, 6 patients with pulmonary TB and tuberculous pleuritis, and 2 patients with pulmonary tuberculoma), BAL fluid (19 patients with pulmonary TB, 6 patients with pulmonary tuberculoma, and 5 patients with miliary TB), pleural fluid (14 patients with tuberculous pleuritis and 2 patients with pulmonary TB and tuberculous pleuritis), resected lymph node (12 patients with cervical tuberculous lymphadenitis), peritoneal fluid (2 patients with tuberculous peritonitis). Acid-fast smear results for samples were positive in 54 of 100 patients (54%) in group 2. The remaining 46 patients had negative acid-fast smear results and positive culture results for TB.

The clinical characteristics of both groups are shown in Table 1 . Compared to group 2, group 1 had a significantly higher percentage of patients with underlying disease, especially nonrespiratory disease. Concerning the laboratory data and chest radiologic findings in the two groups, there were no significant differences in the indicators of immune status, such as peripheral lymphocyte counts or albumin concentrations, nutritional condition, extension of the lesion, or the existence of a cavity.

Comparisons between the results of the TST and the QFT-2G test among 30 elderly patients and 100 younger patients with active TB are shown in Table 2 . Elderly patients with active TB had a significantly higher rate of positive QFT-2G test results (76%) than of positive TST results (27%). However, younger patients with active TB did not show any significant difference between the positive rate on QFT-2G test results (87%) and the positive rate on TST results (70%). A comparison of the results of the TST and QFT-2G test, including the range and median of the maximum diameter of induration of the TST or those of IFN-γ levels of the QFT-2G test between elderly patients and younger patients, is shown in Table 3 . Although group 1 had a significantly lower positive result rate (27%) and lower values for positive results than group 2 (70%) on the TST test, there was no significant difference in the positive rate and the values for positive results on QFT-2G test between group 1 (76%) and group 2 (87%). As for the QFT-2G test, negative findings were more frequent in group 1 (two patients; 7%) than in group 2 (four patients; 4%), but there was no significant difference. The indeterminate result also occurred more frequently in group 1 (five patients; 16%) than in group 2 (nine patients; 9%), but there was no significant difference.

A comparison of QFT-2G test results that were analyzed according to the combined and separate responses to ESAT-6 and CFP-10 antigens between the elderly patient group (group 1) and the group of 100 younger patients (group 2) is shown in Table 4 . Although there was no significant difference in the rate of positive response to ESAT-6 protein antigen only (p = 0.108) or CFP-10 antigen only (p = 0.740) between the two groups, the positive response rate to ESAT-6 protein and CFP-10 antigens in group 1 (13%) was significantly lower than that in group 2 (32%; p = 0.038).

The clinical findings of elderly patients with active TB who had false-negative or indeterminate QFT-2G test results are shown in Table 5 . Although two patients showed false-negative results on the QFT-2G test as well as on the TST, these were both immunocompromised patients with severe underlying disease, and lymphocytopenia was recognized in the peripheral blood of these patients, although nutritional conditions such as total protein or albumin level were comparatively preserved. In one case, the sputum specimen was smear negative and culture positive (1 colony at 8 weeks) for TB on bacteriologic findings, and showed slight extension of the lesion without cavity on radiologic findings. In the other case, pleural effusion was smear negative and culture positive (1 colony at 8 weeks) for TB on bacteriologic findings, and tuberculous pleuritis was diagnosed. While five patients showed indeterminate results on the QFT-2G test, these five also had various underlying diseases, and lymphocytopenia was recognized in the peripheral blood of these patients. Furthermore, nutritional conditions were extremely poor in most of these patients. However, all five patients showed negative results on serologic tests for HIV. Regarding the judgment of the QFT-2G test, two patients were considered to have had negative responses because the positive control of the QFT-2G test was ≥ 0.5 IU/mL. Five patients were considered to have indeterminate results because the positive control for the QFT-2G test was < 0.5 IU/mL. Otherwise, four patients in group 2 showed negative results on the QFT-2G test due to severe underlying diseases and lymphocytopenia, as well as negative results on the TST (the positive control of the QFT-2G test was ≥ 0.5 IU/mL). Nine patients in group 2 showed indeterminate results on the QFT-2G test due to various underlying diseases and lymphocytopenia, as well as negative results on the TST (the positive control for the QFT-2G test was < 0.5 IU/mL).

Whereas the sensitivity of the QFT-2G test for detecting TB infection in patients with untreated culture-confirmed TB was approximately 80% in previous studies,7,9 its sensitivity for detecting TB infection in younger pediatric patients (< 5 years old), elderly patients, or immunocompromised patients has not yet been determined. Recently, Detjen et al12reported that IFN-γ release assays (both the QFT-2G and T-SPOT.TB tests) are useful for diagnosing TB disease in young children. Luetkemeyer et al13and Rangaka et al14 reported that these assays were useful tests for diagnosing TB in immunocompromised patients with HIV infection. However, there have been few reports investigating in detail the clinical usefulness of these tests for elderly patients (ie, those ≥ 80 years old) with active TB. Concerning the QFT-2G test result and the TST result stratified by age, Mori et al,7 reported that while the positive result rates on the QFT-2G test and the TST were 92.3% and 54.5%, respectively, for 13 and 11 patients (approximately 71 to 80 years old), those on the QFT-2G test and the TST were 80.0% and 16.7%, respectively, for 10 and 6 elderly patients (ie, those > 80 years old). That is, the positive result rate on the TST was strikingly decreased in elderly patients with active TB who were > 80 years old. Concerning this finding, we investigated the usefulness of the QFT-2G test as a supportive method for diagnosing TB infection in elderly patients (ie, those ≥ 80 years old) compared to that in younger patients (< 80 years old) in this study. Subsequently, although 27% of elderly patients with active TB had a positive TST result and 77% of this group had a positive QFT-2G result, and there was a significant difference between the results of the TST and THE QFT-2G test, 70% of younger patients with active TB had a positive TST result and 87% had a positive QFT-2G test result. Furthermore, there was no significant difference between TST test and QFT-2G test results in younger patients. Our findings resembled those reported by Mori et al.,7 This study confirmed that the QFT-2G test is a useful method for diagnosing TB infection compared to the TST even for elderly patients (ie, those ≥ 80 years old).

Concerning the combined and separate responses to ESAT-6 protein and CFP-10 antigens in the QFT-2G test, the positive rate for response to both ESAT-6 protein and CFP-10 antigens in elderly patients with active TB was significantly lower than that in younger patients with active TB. Chee et al15reported that 47% of patients were positive for CFP-10 only, 20% of patients were positive for ESAT-6 protein only, and 33% of patients were positive for both antigens when the results were analyzed using combined and separate responses to ESAT-6 protein and CFP-10 antigens in 226 adults suspected of having latent TB infection by results of the T-SPOT.TB assay. The roles of ESAT-6 protein and CFP-10 in TB pathogenesis have not been yet defined. The genes encoding these antigens are transcribed together16; these two proteins form a tight 1:1 complex, and evidence suggests that they are active as a complex.17 As the reason underlying the low positive response rate for both antigens, it may be speculated that the dose of IFN-γ produced by MTB-specific antigens such as those for ESAT-6 protein and/or CFP-10 gradually decreases with aging. However, although we adopted the Centers for Disease Control and Prevention guidelines5 for cutoff values indicating a positive response on the QFT-2G test (ie, levels of either ESAT-6 protein or CFP-10 antigen of ≥ 0.35 IU/mL), there was no problem in judging the results of QFT-2G tests for elderly patients with active TB because the positive rate on the QFT-2G test was significantly higher than that on the TST.

Next, we investigated the reason for indeterminate QFT-2G test results in five patients with active TB and the false-negative QFT-2G test results for two patients with active TB as well as negative TST results in elderly patients with active TB. This finding was the same in younger patients with active TB. These results may become parameters that are linked with negative results on the TST in both groups. All five patients with indeterminate QFT-2G test results showed severe lymphocytopenia (ie, peripheral lymphocyte counts of < 500/μL) due to underlying diseases or aging (Table 5). This QFT-2G test depends on the elaboration of inflammatory cytokines by T cells previously sensitized to MTB-specific antigens. In this test, mononuclear cells from peripheral blood are stimulated in vitro, and the production of IFN-γ from sensitized T cells is measured by the enzyme-linked immunosorbent assay method.2 Therefore, we considered that lymphocytopenia caused a decrease in the production of IFN-γ and lower mitogen QFT-2G test levels (ie, < 0.5 IU/mL). Although there were two patients showing negative QFT-2G results, these patients both showed mild lymphocytopenia (ie, peripheral lymphocyte counts of approximately 300 to 600 IU/mL), differing from the five patients with indeterminate responses to the QFT-2G test. We speculate that the reason for the negative response to the QFT-2G test mainly related to the limited dose of MTB in the sputum culture, the small lesion size, or the presence of tuberculous pleuritis as extrapulmonary TB rather than lymphocytopenia.

In conclusion, this study demonstrated the usefulness of the QFT-2G test as an immunologic diagnostic method for the detection of elderly patients (ie, those ≥ 80 years old) with active TB compared with the TST. However, because several indeterminate QFT-2G test results were encountered among patients with active TB who demonstrated moderate-to-severe lymphocytopenia due to underlying diseases and a few negative QFT-2G test results were encountered in patients with active TB showing a limited dose of MTB in the sputum culture, small lesion size, or the presence of tuberculous pleuritis as extrapulmonary TB, we must take care to identify such patients among elderly patients (ie, those ≥ 80 years old) at the time the QFT-2G test is performed in order to obtain an accurate diagnosis of active TB.

Abbreviations: BCG = bacillus Calmette-Guerin; CFP-10 = culture filtrate protein 10; ESAT-6 = early secretory antigenic target 6-kd; IFN = interferon; MTB = Mycobacterium tuberculosis; QFT-2G = QuantiFERON-TB-2 Gold; TB = tuberculosis; TST = tuberculin skin test

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Table Graphic Jump Location
Table 1. Clinical Characteristics of 30 Elderly Patients (Group 1) and 100 Younger Patients (Group 2)*
* 

Values are given as the mean ± SD or No. (%), unless otherwise indicated.

 

All patients received corticosteroid therapy.

Table Graphic Jump Location
Table 2. Comparison Between the Results of TST and QFT-2G Test Among 30 Elderly Patients With Active TB Disease (Group 1) and 100 Younger Patients With Active TB Disease (Group 2)*
* 

Values are given as %.

Table Graphic Jump Location
Table 3. Comparison of the Results of TST and QFT-2G Test Between 30 Elderly Patients (Group 1) and 100 Younger Patients (Group 2)*
* 

Values are given as No. (%) [range; median], unless otherwise indicated.

 

Values in parenthesis are for comparisons of the positive response rates.

Table Graphic Jump Location
Table 4. Comparison of the Results of QFT-2G Test Analyzed by Combined and Separate Responses to ESAT-6 and CFP-10 Antigens Between Elderly Patients (Group 1) and 100 Younger Patients (Group 2)*
* 

Values are given as No. (%), unless otherwise indicated.

Table Graphic Jump Location
Table 5. Clinical Findings of Elderly Patients With Active TB Disease Who Had False-Negative or Indeterminate QFT-2G Test Results*
* 

AFB = acid-fast bacilli; BALF = BAL fluid; CVD = cerebrovascular disease; MDS = myelodysplastic syndrome; PE = pleural effusion; F = female; M = male; − = negative; + = positive; TP = total protein; Alb = albumin.

 

Data denote portion and cavity finding.

 

Treated with corticosteroid therapy.

Huebner, RE, Scheun, MF, Bass, JB, Jr (1993) The tuberculin skin test.Clin Infect Dis17,968-975. [PubMed] [CrossRef]
 
Andersen, P, Munk, ME, Pollock, JM, et al Specific immune-based diagnosis of tuberculosis.Lancet2000;356,1048-1049. [PubMed]
 
Lalvani, A, Pathan, AA, McShane, H, et al Rapid detection ofMycobacterium tuberculosisinfection by enumeration of antigen-specific T cells.Am J Respir Crit Care Med2001;163,824-828. [PubMed]
 
Pai, M, Riley, LW, Colford, JM Interferon-γ assays in the immunodiagnosis of tuberculosis: a systematic review.Lancet Infect Dis2004;4,761-776. [PubMed]
 
Mazurek, GH, Jereb, J, Lobue, P, et al Guidelines for using the QuantiFERON-TB Gold test for detectingMycobacterium tuberculosisinfection, United States.MMWR Recomm Rep2005;54,49-55. [PubMed]
 
Rothel, JS, Andersen, P Diagnosis of latentMycobacterium tuberculosisinfection: is the demise of the Mantoux test imminent?Expert Rev Anti Infect Ther2005;3,981-993. [PubMed]
 
Mori, T, Sakatani, M, Yamagishi, F, et al Specific detection of tuberculosis infection: an interferon-γ-based assay suing new antigens.Am J Respir Crit Care Med2004;170,59-64. [PubMed]
 
Kobashi, Y, Obase, Y, Fukuda, M, et al Clinical reevaluation of the QuantiFERON TB-2G test as a diagnostic method for differentiating active tuberculosis from nontuberculous mycobacteriosis.Clin Infect Dis2006;43,1540-1546. [PubMed]
 
Brock, I, Weldingh, K, Lillebaek, T, et al Comparison of tuberculin skin test and new specific blood test in tuberculosis contacts.Am J Respir Crit Care Med2004;170,65-69. [PubMed]
 
Richeldi, L An update on the diagnosis of tuberculosis infection.Am J Respir Crit Care Med2006;174,736-742. [PubMed]
 
American Thoracic Society.. Targeted tuberculin testing and treatment of latent tuberculosis infection.Am J Respir Crit Care Med2000;161,S21-S247
 
Detjen, AK, Keil, T, Hauer, B, et al Interferon-γ release assays improve the diagnosis of tuberculosis and nontuberculous mycobacterial disease in children in a country with a low incidence of tuberculosis.Clin Infect Dis2007;45,322-328. [PubMed]
 
Luetkemeyer, AF, Charlebois, ED, Flores, LL, et al Comparison of an interferon-γ release assay with tuberculin skin testing in HIV-infected individuals.Am J Respir Crit Care Med2007;175,737-742. [PubMed]
 
Rangaka, MX, Wilkinson, KA, Seldon, R, et al Effect of HIV-1 infection on T-cell-based and skin test detection of tuberculosis infection.Am J Respir Crit Care Med2007;175,514-520. [PubMed]
 
Chee, CBE, KhinMar, KW, Gan, SH, et al Latent tuberculosis infection treatment and T-cell responses toMycobacterium tuberculosis-specific antigens.Am J Respir Crit Care Med2007;175,282-287. [PubMed]
 
Berther, FX, Rasmussen, PB, Rosenkrands, I, et al AMycobacterium tuberculosisoperon encoding ESAT-6 and a novel low-molecular-mass culture filtrate protein (CFP-10).Microbiology1998;144,3195-3203. [PubMed]
 
Renshaw, PS, Panagiotidou, P, Whelan, A, et al Conclusive evidence that the major T-cell antigens of theMycobacterium tuberculosiscomplex ESAT-6 and CFP-10 form a tight, 1:1 complex and characterization of the structural properties of ESAT-6, CFP-10, and the ESAT-6.CFP-10 complex.J Biol Chem2002;277,21598-21603. [PubMed]
 

Figures

Tables

Table Graphic Jump Location
Table 1. Clinical Characteristics of 30 Elderly Patients (Group 1) and 100 Younger Patients (Group 2)*
* 

Values are given as the mean ± SD or No. (%), unless otherwise indicated.

 

All patients received corticosteroid therapy.

Table Graphic Jump Location
Table 2. Comparison Between the Results of TST and QFT-2G Test Among 30 Elderly Patients With Active TB Disease (Group 1) and 100 Younger Patients With Active TB Disease (Group 2)*
* 

Values are given as %.

Table Graphic Jump Location
Table 3. Comparison of the Results of TST and QFT-2G Test Between 30 Elderly Patients (Group 1) and 100 Younger Patients (Group 2)*
* 

Values are given as No. (%) [range; median], unless otherwise indicated.

 

Values in parenthesis are for comparisons of the positive response rates.

Table Graphic Jump Location
Table 4. Comparison of the Results of QFT-2G Test Analyzed by Combined and Separate Responses to ESAT-6 and CFP-10 Antigens Between Elderly Patients (Group 1) and 100 Younger Patients (Group 2)*
* 

Values are given as No. (%), unless otherwise indicated.

Table Graphic Jump Location
Table 5. Clinical Findings of Elderly Patients With Active TB Disease Who Had False-Negative or Indeterminate QFT-2G Test Results*
* 

AFB = acid-fast bacilli; BALF = BAL fluid; CVD = cerebrovascular disease; MDS = myelodysplastic syndrome; PE = pleural effusion; F = female; M = male; − = negative; + = positive; TP = total protein; Alb = albumin.

 

Data denote portion and cavity finding.

 

Treated with corticosteroid therapy.

References

Huebner, RE, Scheun, MF, Bass, JB, Jr (1993) The tuberculin skin test.Clin Infect Dis17,968-975. [PubMed] [CrossRef]
 
Andersen, P, Munk, ME, Pollock, JM, et al Specific immune-based diagnosis of tuberculosis.Lancet2000;356,1048-1049. [PubMed]
 
Lalvani, A, Pathan, AA, McShane, H, et al Rapid detection ofMycobacterium tuberculosisinfection by enumeration of antigen-specific T cells.Am J Respir Crit Care Med2001;163,824-828. [PubMed]
 
Pai, M, Riley, LW, Colford, JM Interferon-γ assays in the immunodiagnosis of tuberculosis: a systematic review.Lancet Infect Dis2004;4,761-776. [PubMed]
 
Mazurek, GH, Jereb, J, Lobue, P, et al Guidelines for using the QuantiFERON-TB Gold test for detectingMycobacterium tuberculosisinfection, United States.MMWR Recomm Rep2005;54,49-55. [PubMed]
 
Rothel, JS, Andersen, P Diagnosis of latentMycobacterium tuberculosisinfection: is the demise of the Mantoux test imminent?Expert Rev Anti Infect Ther2005;3,981-993. [PubMed]
 
Mori, T, Sakatani, M, Yamagishi, F, et al Specific detection of tuberculosis infection: an interferon-γ-based assay suing new antigens.Am J Respir Crit Care Med2004;170,59-64. [PubMed]
 
Kobashi, Y, Obase, Y, Fukuda, M, et al Clinical reevaluation of the QuantiFERON TB-2G test as a diagnostic method for differentiating active tuberculosis from nontuberculous mycobacteriosis.Clin Infect Dis2006;43,1540-1546. [PubMed]
 
Brock, I, Weldingh, K, Lillebaek, T, et al Comparison of tuberculin skin test and new specific blood test in tuberculosis contacts.Am J Respir Crit Care Med2004;170,65-69. [PubMed]
 
Richeldi, L An update on the diagnosis of tuberculosis infection.Am J Respir Crit Care Med2006;174,736-742. [PubMed]
 
American Thoracic Society.. Targeted tuberculin testing and treatment of latent tuberculosis infection.Am J Respir Crit Care Med2000;161,S21-S247
 
Detjen, AK, Keil, T, Hauer, B, et al Interferon-γ release assays improve the diagnosis of tuberculosis and nontuberculous mycobacterial disease in children in a country with a low incidence of tuberculosis.Clin Infect Dis2007;45,322-328. [PubMed]
 
Luetkemeyer, AF, Charlebois, ED, Flores, LL, et al Comparison of an interferon-γ release assay with tuberculin skin testing in HIV-infected individuals.Am J Respir Crit Care Med2007;175,737-742. [PubMed]
 
Rangaka, MX, Wilkinson, KA, Seldon, R, et al Effect of HIV-1 infection on T-cell-based and skin test detection of tuberculosis infection.Am J Respir Crit Care Med2007;175,514-520. [PubMed]
 
Chee, CBE, KhinMar, KW, Gan, SH, et al Latent tuberculosis infection treatment and T-cell responses toMycobacterium tuberculosis-specific antigens.Am J Respir Crit Care Med2007;175,282-287. [PubMed]
 
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