Performance of The Truenat Tuberculosis and Rifampicin-Resistance Assays in the Microscopy Centre: A Prospective Multicentre Diagnostic Accuracy Study

Background: Bringing reliable and accurate tuberculosis (TB) diagnosis closer to patients is a key priority for global TB control. Molbio Diagnostics have developed the Truenat point-of-care molecular assays for detection of TB and rifampicin (RIF) resistance. Methods: We conducted a prospective multicentre study at 19 microscopy centres and seven reference laboratories in Peru, India, Ethiopia and Papua New Guinea to determine the diagnostic accuracy of the Truenat MTB, MTB Plus and MTB-RIF Dx assays in comparison with Xpert MTB/RIF (‘Xpert’) and Xpert MTB/RIF Ultra (‘Ultra’) using culture as the reference standard (NCT03712709). Findings: Of 1,807 enrolled participants with TB signs/symptoms, 24% were culture positive for Mycobacterium tuberculosis , of which 15% were RIF-resistant by phenotypic drug sensitivity testing. In microscopy centres, the pooled sensitivity of Truenat MTB and Truenat MTB Plus was 73% [95% CI: 67, 78] and 80% [95% CI: 75, 84], respectively. Among smear-negative specimens, sensitivities were 36% [95% CI: 27, 47] and 47% [95% CI: 37, 58], respectively. Specificity of Truenat MTB and MTB Plus was 98% [95% CI: 97, 99] and 96% [95% CI: 95, 97], respectively. Sensitivity of Truenat MTB-RIF was 84% [95% CI: 62, 95], and specificity was 95% [95% CI: 90, 97]. Interpretation: Truenat assays have comparable accuracy with Xpert and can be performed in microscopy centres and primary health centres. Funding Statement: Bill & Melinda Gates Foundation (OPP1208706), India TB Research Consortium, Indian Council for Medical Research, Australian Department of Foreign Affairs and Trade via the PNGAus Partnership, and German KfW. Declaration of Interests: APN, AMa, CMd, MR, PN and SGS are employed by the Foundation for Innovative New Diagnostics (FIND). FIND is a not-for-profit foundation that supports the evaluation of publicly prioritized tuberculosis assays and the implementation of WHO-approved (guidance and prequalification) assays using donor grants. FIND has product evaluation agreements with several private sector companies that design diagnostics for tuberculosis and other diseases. These agreements strictly define FIND's independence and neutrality with regard to these private sector companies. All other authors have nothing to declare. Ethics Approval Statement: The study was conducted in accordance with the 1964 Helsinki declaration and its subsequent amendments and approved by the relevant institutional review boards and independent ethics committees. All participants provided informed consent, either written, or if illiterate, as a thumbprint on the consent form signed and dated by an impartial witness.