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

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: The 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. Methods: Individuals with and without ATB and HIV infection were enrolled. Serology and TST results were analyzed per se and in combination with the microbiological data. Results: Among 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. Conclusions: In 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.

Original languageEnglish
Article numbere96367
JournalPLoS One
Volume9
Issue number5
DOIs
Publication statusPublished - 5 May 2014
Externally publishedYes

Fingerprint

Tuberculin
tuberculosis
Assays
Skin
Microscopic examination
Tuberculosis
antigens
Antigens
HIV
assays
Glycolipids
Enzyme-Linked Immunosorbent Assay
enzyme-linked immunosorbent assay
Serology
Tuberculin Test
tuberculin
skin tests
Skin Tests
Microscopy
microscopy

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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

In: PLoS One, Vol. 9, No. 5, e96367, 05.05.2014.

Research output: Contribution to journalArticle

Lagrange, PH, Thangaraj, SK, Dayal, R, Deshpande, A, Ganguly, NK, Girardi, E, Joshi, B, Katoch, K, Katoch, VM, Kumar, M, Lakshmi, V, Leportier, M, Longuet, C, Malladi, SVS, Mukerjee, D, Nair, D, Raja, A, Raman, B, Rodrigues, C, Sharma, P, Singh, A, Singh, S, Sodha, A, Kabeer, BS, Vernet, G & Goletti, D 2014, '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', PLoS One, vol. 9, no. 5, e96367. https://doi.org/10.1371/journal.pone.0096367
Lagrange, Philippe H. ; Thangaraj, Satheesh K. ; Dayal, Rajeshwar ; Deshpande, Alaka ; Ganguly, Nirmal K. ; Girardi, Enrico ; Joshi, Beenu ; Katoch, Kiran ; Katoch, Vishwa M. ; Kumar, Manoj ; Lakshmi, Vemu ; Leportier, Marc ; Longuet, Christophe ; Malladi, Subbalaxmi V S ; Mukerjee, Deepali ; Nair, Deepthi ; Raja, Alamelu ; Raman, Balambal ; Rodrigues, Camilla ; Sharma, Pratibha ; Singh, Amit ; Singh, Sarman ; Sodha, Archana ; Kabeer, Basirudeen S. ; Vernet, Guy ; Goletti, Delia. / 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. In: PLoS One. 2014 ; Vol. 9, No. 5.
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title = "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",
abstract = "Background: The 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. Methods: Individuals with and without ATB and HIV infection were enrolled. Serology and TST results were analyzed per se and in combination with the microbiological data. Results: Among 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. Conclusions: In 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.",
author = "Lagrange, {Philippe H.} and Thangaraj, {Satheesh K.} and Rajeshwar Dayal and Alaka Deshpande and Ganguly, {Nirmal K.} and Enrico Girardi and Beenu Joshi and Kiran Katoch and Katoch, {Vishwa M.} and Manoj Kumar and Vemu Lakshmi and Marc Leportier and Christophe Longuet and Malladi, {Subbalaxmi V S} and Deepali Mukerjee and Deepthi Nair and Alamelu Raja and Balambal Raman and Camilla Rodrigues and Pratibha Sharma and Amit Singh and Sarman Singh and Archana Sodha and Kabeer, {Basirudeen S.} and Guy Vernet and Delia Goletti",
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TY - JOUR

T1 - A toolbox for tuberculosis (TB) diagnosis

T2 - An Indian multi-centric study (2006-2008); evaluation of serological assays based on PGL-Tb1 and ESAT-6/CFP10 antigens for TB diagnosis

AU - Lagrange, Philippe H.

AU - Thangaraj, Satheesh K.

AU - Dayal, Rajeshwar

AU - Deshpande, Alaka

AU - Ganguly, Nirmal K.

AU - Girardi, Enrico

AU - Joshi, Beenu

AU - Katoch, Kiran

AU - Katoch, Vishwa M.

AU - Kumar, Manoj

AU - Lakshmi, Vemu

AU - Leportier, Marc

AU - Longuet, Christophe

AU - Malladi, Subbalaxmi V S

AU - Mukerjee, Deepali

AU - Nair, Deepthi

AU - Raja, Alamelu

AU - Raman, Balambal

AU - Rodrigues, Camilla

AU - Sharma, Pratibha

AU - Singh, Amit

AU - Singh, Sarman

AU - Sodha, Archana

AU - Kabeer, Basirudeen S.

AU - Vernet, Guy

AU - Goletti, Delia

PY - 2014/5/5

Y1 - 2014/5/5

N2 - Background: The 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. Methods: Individuals with and without ATB and HIV infection were enrolled. Serology and TST results were analyzed per se and in combination with the microbiological data. Results: Among 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. Conclusions: In 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.

AB - Background: The 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. Methods: Individuals with and without ATB and HIV infection were enrolled. Serology and TST results were analyzed per se and in combination with the microbiological data. Results: Among 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. Conclusions: In 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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