TY - JOUR
T1 - Development and clinical evaluation of a new multiplex PCR assay for a simultaneous diagnosis of tuberculous and nontuberculous mycobacteria
AU - Sarro, Yeya dit Sadio
AU - Butzler, Matthew A.
AU - Sanogo, Fanta
AU - Kodio, Ousmane
AU - Tolofoudie, Mohamed
AU - Goumane, Mariam S.
AU - Baya, Bocar
AU - Diabate, Seydou
AU - Diallo, Ibrahim Boubacar
AU - Daniogo, Djakaridja
AU - Dembele, Bindongo PP
AU - Camara, Issiaka
AU - Kumar, Alisha
AU - Dembele, Etienne
AU - Kone, Bourahima
AU - Achenbach, Chad J.
AU - Theron, Grant
AU - Ouattara, Khadidia
AU - Toloba, Yacouba
AU - Diarra, Bassirou
AU - Doumbia, Seydou
AU - Taiwo, Babafemi
AU - Holl, Jane L.
AU - Murphy, Robert L.
AU - Diallo, Souleymane
AU - McFall, Sally M.
AU - Maiga, Mamoudou
N1 - Funding Information:
This work was supported by the Institute of Global Health of Northwestern University (Catalyzer Fund) and the U.S. National Institutes of Health (R03AI137674, U54EB027049, D43TW010350 and UM1AI069471). We would like to thank all the study participants and the TB unit of the Referral Health Center 4, 5 and 6 of Bamako, the Pulmonary Department of Teaching Hospital of Point G, and the National Institute of Public (INSP) for contributing to patient recruitment and follow-ups during the study. We also thank the team of the University Clinical Research Center (UCRC) of the University of Sciences, techniques, Technologies of Bamako (USTTB) for their valuable scientific and technical assistance during the study. All data and code used for producing the results are freely available for others upon request. Request can be sent to these emails: mamoudou.maiga@northwestern.edu and/or sadio@icermali.org.
Funding Information:
This work was supported by the Institute of Global Health of Northwestern University ( Catalyzer Fund ) and the U.S. National Institutes of Health ( R03AI137674 , U54EB027049 , D43TW010350 and UM1AI069471 ). We would like to thank all the study participants and the TB unit of the Referral Health Center 4, 5 and 6 of Bamako, the Pulmonary Department of Teaching Hospital of Point G, and the National Institute of Public (INSP) for contributing to patient recruitment and follow-ups during the study. We also thank the team of the University Clinical Research Center (UCRC) of the University of Sciences, techniques, Technologies of Bamako (USTTB) for their valuable scientific and technical assistance during the study.
Publisher Copyright:
© 2021 The Author(s)
PY - 2021/8
Y1 - 2021/8
N2 - Background: The prevalence of non-tuberculous mycobacteria (NTM) has been increasing worldwide in both developed and developing countries. NTM infection is clinically indistinguishable from tuberculosis and therefore poses significant challenges in patient management, especially in patients chronically treated for pulmonary TB. In this study, we evaluated a new highly sensitive Multiplex MTB/NTM assay that can differentiate M. tuberculosis complex (MTBC) from all NTM, including the treatable and most common NTM, M. avium complex (MAC). Methods: We developed and optimized a new open- Multiplex MTB/NTM assay with two gene-targets for MTBC (IS6110/senX3-regX3) and two targets for MAC (IS1311/DT1) with samples spiked with stored strains and testing 20 replicates. Patients with presumptive TB and NTM were enrolled at the Respiratory Disease Department of The University Teaching Hospital of Point G, in Mali. Findings: In the development stage, the new assay showed a high analytic performance with 100% detections of MTBC and MAC at only 5 colony forming units (CFUs). Overall, without the treatment failure cases, the Multiplex assay and the Xpert showed a sensitivity, specificity, PPV and NPV of 83·3% [66·4-92·6], 96·6% [88·6-99·0], 92·5% [82·3-96·5] and 92·2% [82·7-96·5] and the Xpert had values of 96·7% [83·3-99·4], 80·0% [68·2-88·1], 70·7 [55·5-82·3] and 97·9% [89·3-99·6], respectively. The Multiplex assay successfully detected all (5/5) the MAC cases. Interpretation: Our new Multiplex assay demonstrates better specificity than Xpert for all group studied, in addition to detecting potential NTM cases. The assay could therefore complement the widely used Xpert assay and enhance discrimination of TB and NTM infections. Funding: This work was supported by the National Institutes of Health (R03AI137674, U54EB027049, D43TW010350 and UM1AI069471) and Northwestern University's Institute for Global Health Catalyzer Fund.
AB - Background: The prevalence of non-tuberculous mycobacteria (NTM) has been increasing worldwide in both developed and developing countries. NTM infection is clinically indistinguishable from tuberculosis and therefore poses significant challenges in patient management, especially in patients chronically treated for pulmonary TB. In this study, we evaluated a new highly sensitive Multiplex MTB/NTM assay that can differentiate M. tuberculosis complex (MTBC) from all NTM, including the treatable and most common NTM, M. avium complex (MAC). Methods: We developed and optimized a new open- Multiplex MTB/NTM assay with two gene-targets for MTBC (IS6110/senX3-regX3) and two targets for MAC (IS1311/DT1) with samples spiked with stored strains and testing 20 replicates. Patients with presumptive TB and NTM were enrolled at the Respiratory Disease Department of The University Teaching Hospital of Point G, in Mali. Findings: In the development stage, the new assay showed a high analytic performance with 100% detections of MTBC and MAC at only 5 colony forming units (CFUs). Overall, without the treatment failure cases, the Multiplex assay and the Xpert showed a sensitivity, specificity, PPV and NPV of 83·3% [66·4-92·6], 96·6% [88·6-99·0], 92·5% [82·3-96·5] and 92·2% [82·7-96·5] and the Xpert had values of 96·7% [83·3-99·4], 80·0% [68·2-88·1], 70·7 [55·5-82·3] and 97·9% [89·3-99·6], respectively. The Multiplex assay successfully detected all (5/5) the MAC cases. Interpretation: Our new Multiplex assay demonstrates better specificity than Xpert for all group studied, in addition to detecting potential NTM cases. The assay could therefore complement the widely used Xpert assay and enhance discrimination of TB and NTM infections. Funding: This work was supported by the National Institutes of Health (R03AI137674, U54EB027049, D43TW010350 and UM1AI069471) and Northwestern University's Institute for Global Health Catalyzer Fund.
KW - Nontuberculous mycobacteria
KW - Simultaneous diagnosis
KW - Tuberculosis
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U2 - 10.1016/j.ebiom.2021.103527
DO - 10.1016/j.ebiom.2021.103527
M3 - Article
C2 - 34391092
AN - SCOPUS:85112285748
SN - 2352-3964
VL - 70
JO - EBioMedicine
JF - EBioMedicine
M1 - 103527
ER -
