Application of Venn's diagram in the diagnosis of pleural tuberculosis using IFN-γ, IP-10 and adenosine deaminase

Santos, Ana Paula; Corrêa, Raquel da Silva; Ribeiro-Alves, Marcelo; Silva, Ana Carolina Oliveira Soares da; Mafort, Thiago Thomáz; Leung, Janaina Aparecida Medeiros; Pereira, Geraldo M. B.; Rodrigues, Luciana Silva; Rufino, Rogério

doi:10.1371/journal.pone.0202481

Cited by 29 publications

(26 citation statements)

References 47 publications

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“…An IFN‐γ concentration above 140 pg/mL has a sensitivity of 94% for TB effusion and a concentration above 240 pg/mL has a sensitivity of 95% . Recently, the combination of high ADA and IFN‐γ was reported to have a specificity and PPV of 100% . The optimal threshold value for identifying tuberculous effusions remains to be identified, and unfortunately the assay remains prohibitively expensive in most environments.…”

Section: Diagnosismentioning

confidence: 99%

“…56,64 Recently, the combination of high ADA and IFN-γ was reported to have a specificity and PPV of 100%. 65 The optimal threshold value for identifying tuberculous effusions remains to be identified, and unfortunately the assay remains prohibitively expensive in most environments. A commercially available costeffective assay is currently being developed.…”

Section: Tb Effusionmentioning

confidence: 99%

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Tuberculous pleural effusion

2019

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Tuberculous effusion is a common disease entity with a spectrum of presentations from a largely benign effusion, which resolves completely, to a complicated effusion with loculations, pleural thickening and even frank empyema, all of which may have a lasting effect on lung function. The pathogenesis is a combination of true pleural infection and an effusive hypersensitivity reaction, compartmentalized within the pleural space. Diagnostic thoracentesis with thorough pleural fluid analysis including biomarkers such as adenosine deaminase and gamma interferon achieves high accuracy in the correct clinical context. Definitive diagnosis may require invasive procedures to demonstrate histological evidence of caseating granulomas or microbiological evidence of the organism on smear or culture. Drug resistance is an emerging problem that requires vigilance and extra effort to acquire a complete drug sensitivity profile for each tuberculous effusion treated. Nucleic acid amplification tests such as Xpert MTB/RIF can be invaluable in this instance; however, the yield is low in pleural fluid. Treatment consists of standard anti‐tuberculous therapy or a guideline‐based individualized regimen in the case of drug resistance. There is low‐quality evidence that suggests possible benefit from corticosteroids; however, they are not currently recommended due to concomitant increased risk of adverse effects. Small studies report some short‐ and long‐term benefit from interventions such as therapeutic thoracentesis, intrapleural fibrinolytics and surgery but many questions remain to be answered.

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Section: Diagnosismentioning

confidence: 99%

Section: Tb Effusionmentioning

confidence: 99%

Tuberculous pleural effusion

2019

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“…In a study about the TB eye disease, the cutoff of QFT was 2 IU/mL, indicating that the cutoff value that was higher than that provided by the manufacturer should be considered to better identify ocular inflammation that is beneficial for full anti-TB treatment [34]. For the diagnosis of TB pleurisy, QFT had the best performance with a cutoff point of 2.33 IU/mL [35]. Another study about the diagnosis of tuberculous pleurisy pointed out that the optimal cutoff of QFT was 0.73 IU/mL for TB Gold assay in blood assay, 0.82 IU/mL for the cultured pleural fluid assay, and 0.94 IU/mL for isolated pleural cell assay [36].…”

Section: Gastroenterology Research and Practicementioning

confidence: 99%

Diagnostic Value of Interferon-Gamma Release Assays Combined with Multiple Indicators for Tuberculous Peritonitis

Gao

Liu

et al. 2020

Gastroenterology Research and Practice

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Objective. To investigate the diagnostic value of interferon-gamma release assays combined with multiple indicators for tuberculous peritonitis. Methods. Patients who were admitted to the hospital due to suspected tuberculous peritonitis were prospectively included during the 30-month study period. Moreover, healthy individuals were recruited and included in the control group. All the study participants were assessed using various indexes, such as interferon-gamma release assays. Results. A total of 180 patients with suspected tuberculous peritonitis were enrolled, and 24 were excluded. 73 patients with a confirmed diagnosis of tuberculous peritonitis were included in the tuberculous peritonitis group, 83 patients with other diseases in the other-disease control group, and 52 healthy individuals in the control group. Moreover, 83 patients in the other-disease control group and 52 participants in the control group were identified as 135 nontuberculous peritonitis patients. The area under the receiver operating characteristics curve for the QuantiFERON-TB test was 0.851 (95% confidence interval: 0.799–0.903), and the optimal cutoff value was 0.55 IU/mL, which corresponds to a sensitivity and specificity of 86.30% and 80.00%, respectively. The receiver operating characteristic curves for the combination of the QuantiFERON-TB test and the use of erythrocyte sedimentation rate, serum adenosine deaminase level, serum cancer antigen 125 level, and hypersensitive C-reactive protein level had an area under the curve of 0.859 (95% confidence interval: 0.809–0.909), with a sensitivity and specificity of 97.26% and 62.96%, respectively. Conclusions. The combined use of the QuantiFERON-TB test and multiple indexes can significantly improve the accuracy of diagnosing tuberculous peritonitis.

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“…Consequently, the development of a rapid and noninvasive bioassay is essential for the diagnosis of tuberculosis infection status. Different studies have proposed that both individual and/or combined cytokines can act as potential biomarkers in differentiating PTB from LTBI [12,15,19,22,23] as well as for the detection of EPTB [13,14,24]. In this study, we employed RT-qPCR to analyze the relative gene expression of cytokines that were stimulated as a part of the bioassay for discriminating tuberculosis infection status, which offers a better advantage with increased sensitivity and specificity.…”

Section: Discussionmentioning

confidence: 99%

“…QuantiFERON-TB Gold In-Tube (QFT-GIT) test also has a limitation in diagnosing EPTB. Although studies have proposed various diagnostic markers, accurate detection of EPTB remains elusive [13,14]. A previous study has shown that the implementation of combined markers might be useful for distinguishing various infection statuses [15].…”

Section: Introductionmentioning

confidence: 99%

Antigen-Specific Cytokine and Chemokine Gene Expression for Diagnosing Latent and Active Tuberculosis

et al. 2020

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Tuberculosis infection exhibits different forms, namely, pulmonary, extrapulmonary, and latent. Here, diagnostic markers based on the gene expression of cytokines and chemokines for differentiating between tuberculosis infection state(s) were identified. Gene expression of seven cytokines (Interferon gamma (IFN-γ), Interferon gamma-induced protein 10 (IP-10), Interleukin-2 receptor (IL-2R), C-X-C Motif Chemokine Ligand 9 (CXCL-9), Interleukin 10 (IL-10), Interleukin 4 (IL-4), and Tumor Necrosis Factor alpha (TNF-α)) in response to tuberculosis antigen was analyzed using real-time polymerase reaction. The sensitivity and specificity of relative quantification (2^-ΔΔCt) of mRNA expression were analyzed by constructing receiver operating characteristic curves and measuring the area under the curve (AUC) values. Combinations of cytokines were analyzed using the R statistical software package. IFN-γ, IP-10, IL2R, and CXCL-9 showed high expression in latent and active tuberculosis patients (p = 0.001), with a decrease in IL10 expression, and no statistical difference in IL-4 levels among all the groups (p = 0.999). IL-10 differentiated pulmonary tuberculosis patients from latent cases with an AUC of 0.731. IL10 combined with CXCL-9 distinguished pulmonary tuberculosis patients from extrapulmonary cases with a sensitivity, specificity, and accuracy of 85.7%, 73.9%, and 81.0%, respectively. IL-10 together with IP-10 and IL-4 differentiated pulmonary tuberculosis from latent cases with a sensitivity and specificity of 77.1% and 88.1%, respectively. Decision tree analysis demonstrated that IFN-γ IL-2R, and IL-4 can diagnose tuberculosis infection with a sensitivity, specificity, and accuracy of 89.7%, 96.1%, and 92.7%, respectively. A combination of gene expression of cytokines and chemokines might serve as an effective marker to differentiate tuberculosis infection state(s).

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Application of Venn's diagram in the diagnosis of pleural tuberculosis using IFN-γ, IP-10 and adenosine deaminase

Cited by 29 publications

References 47 publications

Tuberculous pleural effusion

Tuberculous pleural effusion

Diagnostic Value of Interferon-Gamma Release Assays Combined with Multiple Indicators for Tuberculous Peritonitis

Antigen-Specific Cytokine and Chemokine Gene Expression for Diagnosing Latent and Active Tuberculosis

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