TY - JOUR
T1 - Multi-country evaluation of RISK6, a 6-gene blood transcriptomic signature, for tuberculosis diagnosis and treatment monitoring
AU - Bayaa, Rim
AU - Ndiaye, Mame Diarra Bousso
AU - Chedid, Carole
AU - Kokhreidze, Eka
AU - Tukvadze, Nestani
AU - Banu, Sayera
AU - Uddin, Mohammad Khaja Mafij
AU - Biswas, Samanta
AU - Nasrin, Rumana
AU - Ranaivomanana, Paulo
AU - the HINTT working group within the GABRIEL network
AU - Raherinandrasana, Antso Hasina
AU - Rakotonirina, Julio
AU - Rasolofo, Voahangy
AU - Delogu, Giovanni
AU - De Maio, Flavio
AU - Goletti, Delia
AU - Endtz, Hubert
AU - Ader, Florence
AU - Hamze, Monzer
AU - Ismail, Mohamad Bachar
AU - Pouzol, Stéphane
AU - Rakotosamimanana, Niaina
AU - Hoffmann, Jonathan
AU - Russomando, Graciela
AU - Acosta, Chyntia Carolina Díaz
AU - Arenas, Rossana
N1 - Funding Information:
We are grateful for the inventors of a patent on RISK6 signature, the SATVI Clinical and Laboratory Team. This work was supported by Fondation Mérieux. We thank the patients and volunteer participants, as well as the local healthcare staff in each clinical site for their excellent assistance. We would like to thank Dr. Matthieu SCHOENHALS head of the immunology of infectious diseases unit of IPM for his assistance.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - There is a crucial need for non-sputum-based TB tests. Here, we evaluate the performance of RISK6, a human-blood transcriptomic signature, for TB screening, triage and treatment monitoring. RISK6 performance was also compared to that of two IGRAs: one based on RD1 antigens (QuantiFERON-TB Gold Plus, QFT-P, Qiagen) and one on recombinant M. tuberculosis HBHA expressed in Mycobacterium smegmatis (IGRA-rmsHBHA). In this multicenter prospective nested case–control study conducted in Bangladesh, Georgia, Lebanon and Madagascar, adult non-immunocompromised patients with bacteriologically confirmed active pulmonary TB (ATB), latent TB infection (LTBI) and healthy donors (HD) were enrolled. ATB patients were followed-up during and after treatment. Blood RISK6 scores were assessed using quantitative real-time PCR and evaluated by area under the receiver-operating characteristic curve (ROC AUC). RISK6 performance to discriminate ATB from HD reached an AUC of 0.94 (95% CI 0.89–0.99), with 90.9% sensitivity and 87.8% specificity, thus achieving the minimal WHO target product profile for a non-sputum-based TB screening test. Besides, RISK6 yielded an AUC of 0.93 (95% CI 0.85–1) with 90.9% sensitivity and 88.5% specificity for discriminating ATB from LTBI. Moreover, RISK6 showed higher performance (AUC 0.90, 95% CI 0.85–0.94) than IGRA-rmsHBHA (AUC 0.75, 95% CI 0.69–0.82) to differentiate TB infection stages. Finally, RISK6 signature scores significantly decreased after 2 months of TB treatment and continued to decrease gradually until the end of treatment reaching scores obtained in HD. We confirmed the performance of RISK6 signature as a triage TB test and its utility for treatment monitoring.
AB - There is a crucial need for non-sputum-based TB tests. Here, we evaluate the performance of RISK6, a human-blood transcriptomic signature, for TB screening, triage and treatment monitoring. RISK6 performance was also compared to that of two IGRAs: one based on RD1 antigens (QuantiFERON-TB Gold Plus, QFT-P, Qiagen) and one on recombinant M. tuberculosis HBHA expressed in Mycobacterium smegmatis (IGRA-rmsHBHA). In this multicenter prospective nested case–control study conducted in Bangladesh, Georgia, Lebanon and Madagascar, adult non-immunocompromised patients with bacteriologically confirmed active pulmonary TB (ATB), latent TB infection (LTBI) and healthy donors (HD) were enrolled. ATB patients were followed-up during and after treatment. Blood RISK6 scores were assessed using quantitative real-time PCR and evaluated by area under the receiver-operating characteristic curve (ROC AUC). RISK6 performance to discriminate ATB from HD reached an AUC of 0.94 (95% CI 0.89–0.99), with 90.9% sensitivity and 87.8% specificity, thus achieving the minimal WHO target product profile for a non-sputum-based TB screening test. Besides, RISK6 yielded an AUC of 0.93 (95% CI 0.85–1) with 90.9% sensitivity and 88.5% specificity for discriminating ATB from LTBI. Moreover, RISK6 showed higher performance (AUC 0.90, 95% CI 0.85–0.94) than IGRA-rmsHBHA (AUC 0.75, 95% CI 0.69–0.82) to differentiate TB infection stages. Finally, RISK6 signature scores significantly decreased after 2 months of TB treatment and continued to decrease gradually until the end of treatment reaching scores obtained in HD. We confirmed the performance of RISK6 signature as a triage TB test and its utility for treatment monitoring.
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U2 - 10.1038/s41598-021-93059-1
DO - 10.1038/s41598-021-93059-1
M3 - Article
AN - SCOPUS:85109178012
VL - 11
SP - 1
EP - 12
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 13646
ER -