Multi-country evaluation of RISK6, a 6-gene blood transcriptomic signature, for tuberculosis diagnosis and treatment monitoring
Abstract 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 G...
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2021
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oai:doaj.org-article:de33777566a645f5adea0e0e7f01b1112021-12-02T18:18:32ZMulti-country evaluation of RISK6, a 6-gene blood transcriptomic signature, for tuberculosis diagnosis and treatment monitoring10.1038/s41598-021-93059-12045-2322https://doaj.org/article/de33777566a645f5adea0e0e7f01b1112021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93059-1https://doaj.org/toc/2045-2322Abstract 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.Rim BayaaMame Diarra Bousso NdiayeCarole ChedidEka KokhreidzeNestani TukvadzeSayera BanuMohammad Khaja Mafij UddinSamanta BiswasRumana NasrinPaulo RanaivomananaAntso Hasina RaherinandrasanaJulio RakotonirinaVoahangy RasolofoGiovanni DeloguFlavio De MaioDelia GolettiHubert EndtzFlorence AderMonzer HamzeMohamad Bachar IsmailStéphane PouzolNiaina RakotosamimananaJonathan HoffmannThe HINTT working group within the GABRIEL networkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) |
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Medicine R Science Q Rim Bayaa Mame Diarra Bousso Ndiaye Carole Chedid Eka Kokhreidze Nestani Tukvadze Sayera Banu Mohammad Khaja Mafij Uddin Samanta Biswas Rumana Nasrin Paulo Ranaivomanana Antso Hasina Raherinandrasana Julio Rakotonirina Voahangy Rasolofo Giovanni Delogu Flavio De Maio Delia Goletti Hubert Endtz Florence Ader Monzer Hamze Mohamad Bachar Ismail Stéphane Pouzol Niaina Rakotosamimanana Jonathan Hoffmann The HINTT working group within the GABRIEL network Multi-country evaluation of RISK6, a 6-gene blood transcriptomic signature, for tuberculosis diagnosis and treatment monitoring |
| description |
Abstract 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. |
| format |
article |
| author |
Rim Bayaa Mame Diarra Bousso Ndiaye Carole Chedid Eka Kokhreidze Nestani Tukvadze Sayera Banu Mohammad Khaja Mafij Uddin Samanta Biswas Rumana Nasrin Paulo Ranaivomanana Antso Hasina Raherinandrasana Julio Rakotonirina Voahangy Rasolofo Giovanni Delogu Flavio De Maio Delia Goletti Hubert Endtz Florence Ader Monzer Hamze Mohamad Bachar Ismail Stéphane Pouzol Niaina Rakotosamimanana Jonathan Hoffmann The HINTT working group within the GABRIEL network |
| author_facet |
Rim Bayaa Mame Diarra Bousso Ndiaye Carole Chedid Eka Kokhreidze Nestani Tukvadze Sayera Banu Mohammad Khaja Mafij Uddin Samanta Biswas Rumana Nasrin Paulo Ranaivomanana Antso Hasina Raherinandrasana Julio Rakotonirina Voahangy Rasolofo Giovanni Delogu Flavio De Maio Delia Goletti Hubert Endtz Florence Ader Monzer Hamze Mohamad Bachar Ismail Stéphane Pouzol Niaina Rakotosamimanana Jonathan Hoffmann The HINTT working group within the GABRIEL network |
| author_sort |
Rim Bayaa |
| title |
Multi-country evaluation of RISK6, a 6-gene blood transcriptomic signature, for tuberculosis diagnosis and treatment monitoring |
| title_short |
Multi-country evaluation of RISK6, a 6-gene blood transcriptomic signature, for tuberculosis diagnosis and treatment monitoring |
| title_full |
Multi-country evaluation of RISK6, a 6-gene blood transcriptomic signature, for tuberculosis diagnosis and treatment monitoring |
| title_fullStr |
Multi-country evaluation of RISK6, a 6-gene blood transcriptomic signature, for tuberculosis diagnosis and treatment monitoring |
| title_full_unstemmed |
Multi-country evaluation of RISK6, a 6-gene blood transcriptomic signature, for tuberculosis diagnosis and treatment monitoring |
| title_sort |
multi-country evaluation of risk6, a 6-gene blood transcriptomic signature, for tuberculosis diagnosis and treatment monitoring |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/de33777566a645f5adea0e0e7f01b111 |
| work_keys_str_mv |
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