A Toolbox for Tuberculosis (TB) Diagnosis: An Indian Multicentric Study (2006–2008). Evaluation of QuantiFERON-TB Gold in Tube for TB Diagnosis

Lagrange, Philippe; Thangaraj, Satheesh K.; Dayal, Rajeshwar; Deshpande, Alaka; Ganguly, Nirmal Kumar; Girardi, Enrico; Joshi, Beenu; Katoch, Kiran; Katoch, Vishwa Mohan; Kumar, Manoj; Lakshmi, V; Leportier, Marc; Longuet, Christophe; Malladi, Subbalaxmi V. S.; Mukerjee, Deepali; Nair, Deepthi; Raja, Alamelu; Raman, Balambal; Rodrigues, Camilla; Sharma, Prafull; Singh, Amit; Singh, Sarman; Sodha, Archana; Kabeer, Basirudeen Syed Ahamed; Vernet, Guy; Goletti, Delia

doi:10.1371/journal.pone.0073579

Cited by 17 publications

(13 citation statements)

References 30 publications

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“…Although T-SPOT.TB showed higher sensitivity than QFT-GIT, a relative increase of 12%, there was no statistical evidence of a difference in sensitivity. The sensitivity of QFT-GIT in the IDEA study was lower than that in other recent studies [29][30][31] (see Appendix 11, Table 74).…”

Section: Comparison Of Diagnostic Accuracy Of T-spottb and Quantifercontrasting

confidence: 60%

Interferon gamma release assays for Diagnostic Evaluation of Active tuberculosis (IDEA): test accuracy study and economic evaluation

Takwoingi

Whitworth

Rees-Roberts

et al. 2019

Health Technol Assess

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Background Interferon gamma release assays (IGRAs) are blood tests recommended for the diagnosis of tuberculosis (TB) infection. There is currently uncertainty about the role and clinical utility of IGRAs in the diagnostic workup of suspected active TB in routine NHS clinical practice. Objectives To compare the diagnostic accuracy and cost-effectiveness of T-SPOT.TB ® (Oxford Immunotec, Abingdon, UK) and QuantiFERON® TB GOLD In-Tube (Cellestis, Carnegie, VIC, Australia) for diagnosis of suspected active TB and to estimate the diagnostic accuracy of second-generation IGRAs. Design Prospective within-patient comparative diagnostic accuracy study. Setting Secondary care. Participants Adults (aged ≥ 16 years) presenting as inpatients or outpatients at 12 NHS hospital trusts in London, Slough, Oxford, Leicester and Birmingham with suspected active TB. Interventions The index tests [T-SPOT.TB and QuantiFERON GOLD In-Tube (QFT-GIT)] and new enzyme-linked immunospot assays utilising novel Mycobacterium tuberculosis antigens (Rv3615c, Rv2654, Rv3879c and Rv3873) were verified against a composite reference standard applied by a panel of clinical experts blinded to IGRA results. Main outcome measures Sensitivity, specificity, predictive values and likelihood ratios were calculated to determine diagnostic accuracy. A decision tree model was developed to calculate the incremental costs and incremental health utilities [quality-adjusted life-years (QALYs)] of changing from current practice to using an IGRA as an initial rule-out test. Results A total of 363 patients had active TB (culture-confirmed and highly probable TB cases), 439 had no active TB and 43 had an indeterminate final diagnosis. Comparing T-SPOT.TB and QFT-GIT, the sensitivities [95% confidence interval (CI)] were 82.3% (95% CI 77.7% to 85.9%) and 67.3% (95% CI 62.1% to 72.2%), respectively, whereas specificities were 82.6% (95% CI 78.6% to 86.1%) and 80.4% (95% CI 76.1% to 84.1%), respectively. T-SPOT.TB was more sensitive than QFT-GIT (relative sensitivity 1.22, 95% CI 1.14 to 1.31; p < 0.001), but the specificities were similar (relative specificity 1.02, 95% CI 0.97 to 1.08; p = 0.3). For both IGRAs the sensitivity was lower and the specificity was higher for human immunodeficiency virus (HIV)-positive than for HIV-negative patients. The most promising novel antigen was Rv3615c. The added value of Rv3615c to T-SPOT.TB was a 9% (95% CI 5% to 12%) relative increase in sensitivity at the expense of specificity, which had a relative decrease of 7% (95% CI 4% to 10%). The use of current IGRA tests for ruling out active TB is unlikely to be considered cost-effective if a QALY was valued at £20,000 or £30,000. For T-SPOT.TB, the probability of being cost-effective for a willingness to pay of £20,000/QALY was 26% and 21%, when patients with indeterminate test results were excluded or included, respectively. In comparison, the QFT-GIT probabilities were 8% and 6%. Although the use of IGRAs is cost saving, the health detriment is large owing to delay in diagnosing active TB, leading to prolonged illness. There was substantial between-patient variation in the tests used in the diagnostic pathway. Limitations The recruitment target for the HIV co-infected population was not achieved. Conclusions Although T-SPOT.TB was more sensitive than QFT-GIT for the diagnosis of active TB, the tests are insufficiently sensitive for ruling out active TB in routine clinical practice in the UK. Novel assays offer some promise. Future work The novel assays require evaluation in distinct clinical settings and in immunosuppressed patient groups. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and the NIHR Health Protection Research Unit in Respiratory Infections, Imperial College London, London, UK.

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Section: Comparison Of Diagnostic Accuracy Of T-spottb and Quantifercontrasting

confidence: 60%

Interferon gamma release assays for Diagnostic Evaluation of Active tuberculosis (IDEA): test accuracy study and economic evaluation

Takwoingi

Whitworth

Rees-Roberts

et al. 2019

Health Technol Assess

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“…This is most likely due to the fact that these two populations of ATB patients were similar regarding their HIV status, as previously reported [46], [47].…”

Section: Discussionsupporting

confidence: 71%

A Toolbox for Tuberculosis (TB) Diagnosis: An Indian Multi-Centric Study (2006-2008); Evaluation of Serological Assays Based on PGL-Tb1 and ESAT-6/CFP10 Antigens for TB Diagnosis

Lagrange

Thangaraj²,

Dayal

et al. 2014

PLoS ONE

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BackgroundThe aim of this multi-centric prospective study in India was to assess the accuracy of a serological test as an additional tool for diagnosing active tuberculosis (ATB). In particular, an assay based on ELISA using a phenolic glycolipid (PGL-Tb1) or a fusion protein (ESAT-6/CFP10) was compared to the tuberculin skin test (TST) and the microbiological results according to HIV status.MethodsIndividuals with and without ATB and HIV infection were enrolled. Serology and TST results were analyzed per se and in combination with the microbiological data.ResultsAmong the 778 ATB patients, 102 were HIV-infected, 316 HIV-uninfected and 360 had an HIV-unknown status. Of the 945 non-ATB subjects, 559 were at low risk (community adults) and 386 at high risk of M. tuberculosis exposure. Among those with ATB, the sensitivity of ELISA-PGL-Tb1 for ATB was higher than that of ELISA-ESAT-6/CFP10, both in HIV-infected (72.3% versus 63.7%, p = 0.29) and HIV-uninfected/HIV-unknown groups (40.5% versus 28.6%; p<0.0001), whereas the specificity was around 91% for both tests. Sensitivity for ATB increased when the results of the two ELISA were combined, reaching 75.5% in the HIV-infected and 50.9% in the group of HIV-uninfected/HIV-unknown ATB, with a significant decrease of the global specificity (83.9%). Analyzing the ELISA results with the microbiological results, we observed that the sensitivity of both serology tests was independent of the ATB patients' smear microscopy (SM) status and grade. Combining the results of SM with both ELISA, the detection of ATB patients significantly increased (p<0.0001), particularly in those with extrapulmonary TB (up to 45.1%) or HIV infection (up to 83.3%). No significant association was observed between TST and serology results.ConclusionsIn this prospective multi-centric study, the combination of two rapid tests, such as SM and serology, might be useful in detecting ATB, especially in HIV-infected patients.

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“…[ 29 ] and in India by Lagrange et al . [ 30 ], where the T-cell IFN-γ responses did not correlate with several measures of the bacterial yield in the sputum of the PTB patients at diagnosis, including SM status and grade, and time to positivity of the liquid culture.…”

Section: Discussionmentioning

confidence: 99%

“…A previous study carried out in India has shown that the cumulative results of the smear microscopy and the 2 immunological tests improved the detection rate of ATB [ 30 ]. Similarly, our study shows a cumulative sensitivity of 97.5% with an increase of the LR for the negative test (9.2), indicating that such triple association may rule out PTB in those who are negative for all 3 tests.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Values of the QuantiFERON-TB Gold In-Tube Assay Carried out in China for Diagnosing Pulmonary Tuberculosis

Xing

Wang

et al. 2015

PLoS ONE

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BackgroundInterferon-release assays (IGRAs) for diagnosing active pulmonary tuberculosis (PTB) are not yet fully validated, particularly in high TB-endemic areas as the People's Republic of China (PRC). The aim of this report was to assess the performance of the QuantiFERON-TB Gold In-tube (QFT-GIT) and tuberculin skin test (TST), in addition to microbiological results, as contributors for diagnosing active PTB in the PRC.Methods/Principal FindingsA total of 300 PTB patients, 41 disease controls (DC) and 59 healthy community controls (HCC) were included prospectively between May 2010 and April 2011 from two provinces of the PRC (Heilongjiang and Zhejiang). The QFT-GIT and TST yielded an overall sensitivity for active TB of 80.9% and 86.2%, and a specificity of 36.6% and 26.8%, respectively. The province of origin and smear microscopy status did not significantly impact the diagnostic values for PTB. However, using the TST with a 10 mm cut-off point, a significantly higher proportion of LTBI was observed in the DC than the HCC (p=0.01). Discordant results between the QFT-GIT and TST were found among 1/3 of the PTB, HCC and DC. Two-thirds of the individuals presented TST-positive/QFT-GIT-negative discordant results. The TST-negative/QFT-GIT-positive result was not associated with age or bacillary load. Cumulative QFT-GIT and TST positive results increased the overall sensitivity (95.9%), but it was associated with a dramatic decrease of the overall specificity (24.8%) leading to a suboptimal PPV (80.1%) and a low NPV (61.1%).Conclusions/SignificanceThe usefulness of the QFT-GIT to diagnose active TB in high TB-endemic countries remains doubtful because like the TST, the QFT-GIT cannot distinguish between LTBI and active TB. Used as single stand-alone tests, both the QFT-GIT and TST have very limited roles in the diagnosis of active PTB. However, the combined use of SM, the TST and QFT-GIT may allow for the exclusion of ATB.

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A Toolbox for Tuberculosis (TB) Diagnosis: An Indian Multicentric Study (2006–2008). Evaluation of QuantiFERON-TB Gold in Tube for TB Diagnosis

Cited by 17 publications

References 30 publications

Interferon gamma release assays for Diagnostic Evaluation of Active tuberculosis (IDEA): test accuracy study and economic evaluation

Interferon gamma release assays for Diagnostic Evaluation of Active tuberculosis (IDEA): test accuracy study and economic evaluation

A Toolbox for Tuberculosis (TB) Diagnosis: An Indian Multi-Centric Study (2006-2008); Evaluation of Serological Assays Based on PGL-Tb1 and ESAT-6/CFP10 Antigens for TB Diagnosis

Diagnostic Values of the QuantiFERON-TB Gold In-Tube Assay Carried out in China for Diagnosing Pulmonary Tuberculosis

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