A prospective multicentre diagnostic accuracy study for the Truenat tuberculosis assays.

Adam Penn-Nicholson,Claudia M Denkinger,Abyot Meaza,Catharina Boehme,Bandana Choudhury,Srikanth Tripathy,Evelyn Lavu,Pamela Nabeta,Camilla Rodrigues,Manjula Singh,Mubin Kazi,Sivaramakrishnan N Gomathi,Sarabjit Chadha,Philipp Du Cros,Sanjay Sarin,Ephrem Tesfaye,Eduardo Gotuzzo,Aurélien Macé ,Raman Gangakhedkar ,Morten Rühwald ,P.g Patel ,César Ugarte-Gil ,Samuel G Schumacher

doi:10.1183/13993003.00526-2021

Abstract

BackgroundBringing 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.MethodsWe conducted a prospective multicentre diagnostic accuracy study at 19 primary healthcare centres and seven reference laboratories in Peru, India, Ethiopia and Papua New Guinea to estimate the diagnostic accuracy of the point-of-care Truenat MTB, MTB Plus and MTB-RIF Dx assays for pulmonary TB using culture and phenotypic drug susceptibility testing as the reference standard, compared with Xpert MTB/RIF or Ultra.ResultsOf 1807 enrolled participants with TB signs/symptoms, 24% were culture-positive for Mycobacterium tuberculosis, of which 15% were RIF-resistant. 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. Sensitivity of Truenat MTB-RIF was 84% (95% CI 62–95%). Truenat assays showed high specificity. Head-to-head comparison in the central reference laboratories suggested that the Truenat assays have similar performance to Xpert MTB/RIF.ConclusionWe found the performance of Molbio's Truenat MTB, MTB Plus and MTB-RIF Dx assays to be comparable to that of the Xpert MTB/RIF assay. Performing the Truenat tests in primary healthcare centres with very limited infrastructure was feasible. These data supported the development of a World Health Organization policy recommendation of the Molbio assays.

Highlights

Effective control of the tuberculosis (TB) epidemic requires rapid diagnosis and initiation of appropriate treatment
A total of 331 participants only had a sputum sample collected at the reference laboratory setting and not at the primary health care centre, and amongst those 21 participants did not have any available culture result
The specificity of the assays in the primary health care centre was equivalent to that seen in the reference laboratory, despite the open nature of the assay

Summary

Introduction

Effective control of the tuberculosis (TB) epidemic requires rapid diagnosis and initiation of appropriate treatment. Bringing rapid and accurate TB and drug resistance diagnostics closer to patients is a key priority for TB control, to reach patients in low-resource settings and avoid existing high rates of pre-treatment loss to follow up [3] This requires robust point-of-care diagnostic tests that are implementable at lower levels of the healthcare system. Xpert® MTB/RIF and Xpert® MTB/RIF Ultra („Ultra‟) ) have revolutionized the diagnosis of both TB and RIF resistance [4, 5], with Xpert MTB/RIF demonstrating pooled sensitivity of 85% (82-88%) and specificity of 98% (94-97%), and Ultra providing slightly higher sensitivity of 88% (85-91%) and slightly lower specificity 96% (94-97%) in a recent systematic review [6] These tests, run on GeneXpert instruments (Cepheid, Sunnyvale, USA), require a temperature-controlled environment, a stable power supply and are susceptible to dust [5, 7,8,9,10], limiting operation to district/sub-district hospital settings.

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