TY - JOUR
T1 - Relevance of QuantiFERON-TB Gold Plus and Heparin-Binding Hemagglutinin Interferon-γ Release Assays for Monitoring of Pulmonary Tuberculosis Clearance
T2 - A Multicentered Study
AU - Chedid, Carole
AU - Kokhreidze, Eka
AU - Tukvadze, Nestani
AU - Banu, Sayera
AU - Uddin, Mohammad Khaja Mafij
AU - Biswas, Samanta
AU - Russomando, Graciela
AU - Acosta, Chyntia Carolina Díaz
AU - Arenas, Rossana
AU - Ranaivomanana, Paulo P.R.
AU - Razafimahatratra, Crisca
AU - Herindrainy, Perlinot
AU - Rakotonirina, Julio
AU - Raherinandrasana, Antso Hasina
AU - Rakotosamimanana, Niaina
AU - Hamze, Monzer
AU - Ismail, Mohamad Bachar
AU - Bayaa, Rim
AU - Berland, Jean Luc
AU - Delogu, Giovanni
AU - De Maio, Flavio
AU - Endtz, Hubert
AU - Ader, Florence
AU - Goletti, Delia
AU - Hoffmann, Jonathan
AU - the HINTT working group within the GABRIEL network
N1 - Funding Information:
We would like to thank all the patients participating in our study, as well as the local healthcare staff in each clinical site. In particular, we are very grateful to Leticia Rojas and Laura Franco, from the Molecular Biology Department at the Instituto de Investigaciones en Ciencias de la Salud (Asunci?n, Paraguay) for their valuable help with patient data collection. Finally, we would like to dedicate this work to the memory of Mar?a Maldonado, from the Hospital General de San Lorenzo (Asunci?n, Paraguay). We are beyond grateful to her for her dedication during the recruitment and follow-up process of the patients in this study, as well as for her unfailing involvement in the fight against tuberculosis in Paraguay.
Publisher Copyright:
© Copyright © 2021 Chedid, Kokhreidze, Tukvadze, Banu, Uddin, Biswas, Russomando, Acosta, Arenas, Ranaivomanana, Razafimahatratra, Herindrainy, Rakotonirina, Raherinandrasana, Rakotosamimanana, Hamze, Ismail, Bayaa, Berland, De Maio, Delogu, Endtz, Ader, Goletti and Hoffmann.
PY - 2021/2/2
Y1 - 2021/2/2
N2 - Background: Tuberculosis (TB) is a leading infectious cause of death. To improve treatment efficacy, quicker monitoring methods are needed. The objective of this study was to monitor the response to a heparin-binding hemagglutinin (HBHA) interferon-γ (IFN-γ) release assay (IGRA) and QuantiFERON-TB Gold Plus (QFT-P) and to analyze plasma IFN-γ levels according to sputum culture conversion and immune cell counts during treatment. Methods: This multicentered cohort study was based in Bangladesh, Georgia, Lebanon, Madagascar, and Paraguay. Adult, non-immunocompromised patients with culture-confirmed pulmonary TB were included. Patients were followed up at baseline (T0), after two months of treatment (T1), and at the end of therapy (T2). Clinical data and blood samples were collected at each timepoint. Whole blood samples were stimulated with QFT-P antigens or recombinant methylated Mycobacterium tuberculosis HBHA (produced in Mycobacterium smegmatis; rmsHBHA). Plasma IFN-γ levels were then assessed by ELISA. Findings: Between December 2017 and September 2020, 132 participants completed treatment, including 28 (21.2%) drug-resistant patients. rmsHBHA IFN-γ increased significantly throughout treatment (0.086 IU/ml at T0 vs. 1.03 IU/ml at T2, p < 0.001) while QFT-P IFN-γ remained constant (TB1: 0.53 IU/ml at T0 vs. 0.63 IU/ml at T2, p = 0.13). Patients with low lymphocyte percentages (<14%) or high neutrophil percentages (>79%) at baseline had significantly lower IFN-γ responses to QFT-P and rmsHBHA at T0 and T1. In a small group of slow converters (patients with positive cultures at T1; n = 16), we observed a consistent clinical pattern at baseline (high neutrophil percentages, low lymphocyte percentages and BMI, low TB1, TB2, and MIT IFN-γ responses) and low rmsHBHA IFN-γ at T1 and T2. However, the accuracy of the QFT-P and rmsHBHA IGRAs compared to culture throughout treatment was low (40 and 65% respectively). Combining both tests improved their sensitivity and accuracy (70–80%) but not their specificity (<30%). Conclusion: We showed that QFT-P and rmsHBHA IFN-γ responses were associated with rates of sputum culture conversion. Our results support a growing body of evidence suggesting that rmsHBHA IFN-γ discriminates between the different stages of TB, from active disease to controlled infection. However, further work is needed to confirm the specificity of QFT-P and rmsHBHA IGRAs for treatment monitoring.
AB - Background: Tuberculosis (TB) is a leading infectious cause of death. To improve treatment efficacy, quicker monitoring methods are needed. The objective of this study was to monitor the response to a heparin-binding hemagglutinin (HBHA) interferon-γ (IFN-γ) release assay (IGRA) and QuantiFERON-TB Gold Plus (QFT-P) and to analyze plasma IFN-γ levels according to sputum culture conversion and immune cell counts during treatment. Methods: This multicentered cohort study was based in Bangladesh, Georgia, Lebanon, Madagascar, and Paraguay. Adult, non-immunocompromised patients with culture-confirmed pulmonary TB were included. Patients were followed up at baseline (T0), after two months of treatment (T1), and at the end of therapy (T2). Clinical data and blood samples were collected at each timepoint. Whole blood samples were stimulated with QFT-P antigens or recombinant methylated Mycobacterium tuberculosis HBHA (produced in Mycobacterium smegmatis; rmsHBHA). Plasma IFN-γ levels were then assessed by ELISA. Findings: Between December 2017 and September 2020, 132 participants completed treatment, including 28 (21.2%) drug-resistant patients. rmsHBHA IFN-γ increased significantly throughout treatment (0.086 IU/ml at T0 vs. 1.03 IU/ml at T2, p < 0.001) while QFT-P IFN-γ remained constant (TB1: 0.53 IU/ml at T0 vs. 0.63 IU/ml at T2, p = 0.13). Patients with low lymphocyte percentages (<14%) or high neutrophil percentages (>79%) at baseline had significantly lower IFN-γ responses to QFT-P and rmsHBHA at T0 and T1. In a small group of slow converters (patients with positive cultures at T1; n = 16), we observed a consistent clinical pattern at baseline (high neutrophil percentages, low lymphocyte percentages and BMI, low TB1, TB2, and MIT IFN-γ responses) and low rmsHBHA IFN-γ at T1 and T2. However, the accuracy of the QFT-P and rmsHBHA IGRAs compared to culture throughout treatment was low (40 and 65% respectively). Combining both tests improved their sensitivity and accuracy (70–80%) but not their specificity (<30%). Conclusion: We showed that QFT-P and rmsHBHA IFN-γ responses were associated with rates of sputum culture conversion. Our results support a growing body of evidence suggesting that rmsHBHA IFN-γ discriminates between the different stages of TB, from active disease to controlled infection. However, further work is needed to confirm the specificity of QFT-P and rmsHBHA IGRAs for treatment monitoring.
KW - heparin-binding haemagglutinin adhesin
KW - immunomonitoring
KW - inflammatory markers
KW - interferon-gamma release assays
KW - QuantiFERON
KW - treatment monitoring
KW - tuberculosis
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U2 - 10.3389/fimmu.2020.616450
DO - 10.3389/fimmu.2020.616450
M3 - Article
C2 - 33603746
AN - SCOPUS:85100917779
VL - 11
SP - 1
EP - 11
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
M1 - 616450
ER -