Inadequate values from an interferon-gamma release assay for smear-negative tuberculosis in a high-burden setting

F, Liu; Fj, Du; Hy, Jia; Lp, Pan; Zhang, X; Ay, Xing; Bp, Du; Sun, Qing‐Yuan; Lh, Nie; H, Li; Rm, Liu; Ma, Yingmin; Zd, Zhang

doi:10.5588/ijtld.14.0233

Cited by 6 publications

(4 citation statements)

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“…In the present study, age ≤ 35 years and positive IGRAs results were predictive factors for positive BALF results. Although IGRAs cannot reliably distinguish active TB from latent TB infection, we and other researchers have shown that the levels of IFN-γ determined by IGRAs are associated with sputum Mtb positivity in immune competent pulmonary TB patients [20], and the sensitivity of IGRAs is correlated with paucibacillary nature of the samples [21]. In line with these findings, here we found IGRAs alone has a predictive odds ratio of 3.743 (95% CI: 2.478–5.655) for Mtb positivity in BALF, due to the existence Non-TB patients in the BALF-negative TB suspects.…”

Section: Discussionmentioning

confidence: 99%

Indicators for prediction of Mycobacterium tuberculosis positivity detected with bronchoalveolar lavage fluid

et al. 2018

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BackgroundThe diagnosis of active pulmonary tuberculosis (TB) remains a challenge in clinic, especially for sputum negative pulmonary TB. Bronchoalveolar lavage fluid (BALF) has higher sensitivity than sputum for detection of Mycobacterium tuberculosis (Mtb). However, bronchoscopy is invasive and costly, and not suitable for all patients. In order to make TB patients get more benefit from BALF for diagnosis, we explore which indicator might be used to optimize the choice of bronchoscopy.MethodsA total of 1539 sputum-smear-negative pulmonary TB suspects who underwent bronchoscopy were recruited for evaluation. The sensitivity, specificity and accuracy of Mtb detection in sputum and BALF were compared. Odds ratios and 95% confidence intervals were used to assess variables that associated with positive acid-fast bacilli (AFB) smear, Mtb culture and nucleic acid amplification test (NAAT) of BALF in sputum-negative and non-sputum-producing pulmonary TB suspects.ResultsBALF has significantly higher sensitivity (63.4%) than sputum (43.5%) for Mtb detection by culture and NAAT. 19.7% (122/620) sputum-negative and 40.0% (163/408) non-sputum-producing suspects had positive bacteriological results in BALF. Among sputum-negative and non-sputum-producing pulmonary TB suspects, the positivity of Mtb detection in BALF is associated with a younger age, the presence of pulmonary cavities and a positive result of interferon-gamma release assay (IGRA). Sputum-negative patients under 35 years old with positive IGRA and pulmonary cavity had 84.8% positivity of Mtb in BALF.ConclusionsOur study indicated that combination of age, the presence of pulmonary cavity, and the result of IGRA is useful to predict the positivity of Mtb detection in BALF among sputum-negative and non-sputum producing pulmonary TB suspects. Those who are under 35 years old, positive for the presence of pulmonary cavity and IGRA, should undergo bronchoscopy to collect BAFL for Mtb tests, as they have the highest possibility to get bacteriologically confirmation of TB.Electronic supplementary materialThe online version of this article (10.1186/s40249-018-0403-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Indicators for prediction of Mycobacterium tuberculosis positivity detected with bronchoalveolar lavage fluid

et al. 2018

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“…(94.7%),[ 7 ] and Liu et al . (93.2%),[ 21 ] and in one study from India (90.6%). [ 9 ] From the ten reported studies evaluating T-SPOT.TB in China, the combined sensitivity was 88%.…”

Section: Discussionmentioning

confidence: 99%

Interferon-Gamma Release Assay is Not Appropriate for the Diagnosis of Active Tuberculosis in High-Burden Tuberculosis Settings

Kang

Wang

M³

et al. 2018

Chinese Medical Journal

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Background:Interferon-gamma release assay (IGRA) has been used in latent tuberculosis (TB) infection and TB diagnosis, but the results from different high TB-endemic countries are different. The aim of this study was to investigate the value of IGRA in the diagnosis of active pulmonary TB (PTB) in China.Methods:We conducted a large-scale retrospective multicenter investigation to further evaluate the role of IGRA in the diagnosis of active PTB in high TB-epidemic populations and the factors affecting the performance of the assay. All patients who underwent valid T-SPOT.TB assays from December 2012 to November 2015 in six large-scale specialized TB hospitals in China and met the study criteria were retrospectively evaluated. Patients were divided into three groups: Group 1, sputum culture-positive PTB patients, confirmed by positive Mycobacterium tuberculosis sputum culture; Group 2, sputum culture-negative PTB patients; and Group 3, non-TB respiratory diseases. The medical records of all patients were collected. Chi-square tests and Fisher's exact test were used to compare categorical data. Multivariable logistic analyses were performed to evaluate the relationship between the results of T-SPOT in TB patients and other factors.Results:A total of 3082 patients for whom complete information was available were included in the investigation, including 905 sputum culture-positive PTB cases, 914 sputum culture-negative PTB cases, and 1263 non-TB respiratory disease cases. The positive rate of T-SPOT.TB was 93.3% in the culture-positive PTB group and 86.1% in the culture-negative PTB group. In the non-PTB group, the positive rate of T-SPOT.TB was 43.6%. The positive rate of T-SPOT.TB in the culture-positive PTB group was significantly higher than that in the culture-negative PTB group (χ2 = 25.118, P < 0.01), which in turn was significantly higher than that in the non-TB group (χ2 = 566.116, P < 0.01). The overall results were as follows: sensitivity, 89.7%; specificity, 56.37%; positive predictive value, 74.75%; negative predictive value, 79.11%; and accuracy, 76.02%.Conclusions:High false-positive rates of T-SPOT.TB assays in the non-TB group limit the usefulness as a single test to diagnose active TB in China. We highly recommend that IGRAs not be used for the diagnosis of active TB in high-burden TB settings.

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“…In addition, FCN2 levels were significantly increased in smear-positive patients compared with smear-negative patients ( P = 0.016, Table 3 ). We assumed that smear-negative patients had a higher proportion of latent infections 40 , resulting in limited complement system activation and reduced FCN2 levels.…”

Section: Discussionmentioning

confidence: 99%

Screening and identification of five serum proteins as novel potential biomarkers for cured pulmonary tuberculosis

Wang

Wei

Shi

et al. 2015

Sci Rep

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Rapid and efficient methods for the determination of cured tuberculosis (TB) are lacking. A total of 85 differentially expressed serum proteins were identified by iTRAQ labeling coupled with two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) analysis (fold change >1.50 or <0.60, P < 0.05). We validated albumin (ALB), Rho GDP-dissociation inhibitor 2 (ARHGDIB), complement 3 (C3), ficolin-2 (FCN2), and apolipoprotein (a) (LPA) using the enzyme-linked immunosorbent assay (ELISA) method. Significantly increased ALB and LPA levels (P = 0.036 and P = 0.012, respectively) and significantly reduced ARHGDIB, C3, and FCN2 levels (P < 0.001, P = 0.035, and P = 0.018, respectively) were observed in cured TB patients compared with untreated TB patients. In addition, changes in ALB and FCN2 levels occurred after 2 months of treatment (P < 0.001 and P = 0.030, respectively). We established a cured TB model with 87.10% sensitivity, 79.49% specificity, and an area under the curve (AUC) of 0.876. The results indicated that ALB, ARHGDIB, C3, FCN2, and LPA levels might serve as potential biomarkers for cured TB. Our study provides experimental data for establishing objective indicators of cured TB and also proposes potential markers for evaluating the efficacy of anti-TB drugs.

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Inadequate values from an interferon-gamma release assay for smear-negative tuberculosis in a high-burden setting

Cited by 6 publications

References 0 publications

Indicators for prediction of Mycobacterium tuberculosis positivity detected with bronchoalveolar lavage fluid

Indicators for prediction of Mycobacterium tuberculosis positivity detected with bronchoalveolar lavage fluid

Interferon-Gamma Release Assay is Not Appropriate for the Diagnosis of Active Tuberculosis in High-Burden Tuberculosis Settings

Screening and identification of five serum proteins as novel potential biomarkers for cured pulmonary tuberculosis

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