Multicentric validation of indigenous molecular test Truenat™ MTB for detection of Mycobacterium tuberculosis in sputum samples from presumptive pulmonary tuberculosis patients in comparison with reference standards

Abstract

Background & objectives: Early case detection is essential to interrupt transmission and to prevent further spread of tuberculosis (TB) in high endemic settings. Nucleic acid amplification tests (NAATs) with visual read-outs are ideal as point-of-care tests. Truenat™ MTB is an indigenous chip-based NAAT for detection of Mycobacterium tuberculosis , which involves extraction of DNA and real-time polymerase chain reaction (PCR) using portable, automated, battery-operated instruments. The current multicentric study was aimed to evaluate Truenat for detection of MTB in sputum samples obtained from patients with presumptive pulmonary TB with reference to culture as gold standard and Xpert as a comparator. Methods: The study was conducted at four sites, namely ICMR-National Institute for Research in Tuberculosis, Chennai; All India Institute of Medical Sciences, New Delhi; ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra; and National Institute of TB and Respiratory Diseases, New Delhi. Patients suspected to have TB were screened for eligibility. Two sputum samples were collected from each patient. Tests included smear, Xpert and Truenat directly from the sputum sample and culture by Lowenstein-Jensen (L-J) medium and MGIT960 from decontaminated pellets. Sample used for Truenat assay was coded. Resolution of Truenat false positives was done using an in-house PCR with TRC 4 primers. Results: The study enrolled 2419 presumptive TB patients after screening 2465 patients, and 3541 sputum samples were collected from the enrolled patients. Results of 2623 samples were available for analysis. Truenat showed a positivity rate of 48.5 per cent as compared to 37.0 per cent by Xpert. The sensitivities of Truenat and Xpert were was 88.3 and 79.7 per cent, respectively in comparison with culture. Interpretation & conclusions: Truenat MTB identified more positives among culture-confirmed samples than Xpert and had higher sensitivity. In addition, other advantageous operational features of Truenat MTB were identified which would be useful in field settings.

Expedited diagnosis of pediatric tuberculosis using Truenat MTB-Rif Dx and GeneXpert MTB/RIF

“…The current study demonstrated lower sensitivity but comparable specificity in children as compared to earlier studies in adults, Truenat MTB-RIF Dx demonstrated sensitivity and specificity of 88.3% and 73.8% for detection of MTB in adults 2 . The sensitivity and specificity for detection of Rif resistance in one study was 87.5% and 99.5% respectively 9 .…”

“…However, GeneXpert requires a highly sophisticated laboratory with ambient temperature between 15 and 30 °C, stable electricity supply, and adequate storage space for the cartridges (storage at 2–28 °C), thereby, limiting its use to district hospital settings. Certain newer NAATs have shown promise in studies done in older patients 2 . MolBio Diagnostics (Goa, India) developed three different assays namely Truenat MTB, Truenat MTB Plus and Truenat MTB-RIF Dx based on chip-based real-time Polymerase Chain Reaction (PCR) that utilizes nrdB gene (Truenat MTB), nrdz and IS6110 gene (Truenat MTB Plus) for the semi-quantitative detection of Mycobacterium tuberculosis (MTB) and rpoB gene (Truenat MTB-RIF Dx) for the detection of rifampicin resistance.…”

Performance evaluation of Truenat MTB and Truenat MTB-RIF DX assays in comparison to gene XPERT MTB/RIF ultra for the diagnosis of pulmonary tuberculosis in Uganda

“…Our study documented comparable Truenat sensitivity done on the same sample under primary health care to that documented in a multicenter diagnostic accuracy study [ 7 ]. However, slightly lower sensitivity of Truenat MTB Plus has been documented compared to other previous studies [ 8 , 9 ] possibly and partly attributed to the fact that these studies analyzed two sputum samples rather than one spot sample in our study, which is routinely done in Uganda, and were largely not done in primary health care centers. In addition, these previous studies had a different composition of smear negative but culture positive individuals than in our study.…”

Predisposing, enabling, and need factors influencing rapid uptake of the World Health Organization-endorsed TB diagnostic technologies in Africa

“…In 2020, a new molecular TB diagnostic tool named Truenat (MTB, MTB Plus, and MTB-RIF) was developed by Molbio Diagnostics, Bangalore, India for the detection of TB and RIF-resistance from sputum samples within an hour, and Truenat MTB identified more positives among culture-confirmed samples than Xpert and had higher sensitivity. 25…”

“…In 2020, a new molecular TB diagnostic tool named Truenat (MTB, MTB Plus, and MTB-RIF) was developed by Molbio Diagnostics, Bangalore, India for the detection of TB and RIF-resistance from sputum samples within an hour, and Truenat MTB identified more positives among culture-confirmed samples than Xpert and had higher sensitivity. 25 Despite all these technologies being in place for several years, their reported uptake in high TB burden countries remains low and the factors influencing their uptake are unknown. Our study aimed at documenting the status of the uptake and PEN factors influencing the uptake of WHOendorsed TB diagnostic technologies in the 47 member states of WHO/AFR considering TB diagnostic technologies endorsed by WHO between 2007-2021.…”