-->-->PONE-D-26-00956-->-->Diagnostic accuracy, operational feasibility, and cost considerations of Truenat MTB Plus and Xpert MTB/RIF Ultra for pulmonary tuberculosis-->-->PLOS One

Dear Dr. Sidiq

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Overall Assessment:

The manuscript addresses an important topic in tuberculosis diagnostics and provides useful comparative data between two WHO-recommended molecular platforms. With minor clarifications and additional methodological details, the study could provide valuable insights for diagnostic laboratories and TB control programs.-->-->

Decision:  Minor Revision

Recommendations:

1. The introduction could be expanded  with additional background on molecular diagnostics for TB and supported with relevant references.
2. Please provide the manufacturer details and catalog numbers  of the kits used for both assays.
3. The rifampicin resistance targets for the TruPCR assay  are not described in the introduction and should be included.
4. Additional methodological clarity on both platforms would be helpful. Please clarify whether the assay follows a two-step approach  (initial MTB detection followed by a second PCR for RIF resistance if MTB is positive). For GeneXpert , the specific gene targets used for MTB detection and rifampicin resistance  should also be described.
5. Minor editorial correction required in line 235 (“TB diagnosis of TB” – repetition). Supporting references comparing molecular assays with smear microscopy  would strengthen this statement.
6. In the limitations section , the authors may consider clarifying whether smear-negative or extrapulmonary samples  were included, as assay performance can vary in low bacillary load specimens.

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We look forward to receiving your revised manuscript.

Kind regards,

Dr. Minal Dakhave

Academic Editor

PLOS One

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Reviewers' comments:

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #2: Yes

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Reviewer #1:  I have reviewed the manuscript and made the comments below;

1) The author needs to define feasibility from the beginning. Which parameters were used to measure feasibility?

2) L52-54: This is discussing results, it should be reserved to the conclusion section

3) L57: There are no results for smear microscopy, yet it makes it to the conclusion section

4) L78: please use 2025 WHO TB report for 2024 data

5) 106: The prospective nature of the study design, is not clearly spelt out: how it will be done and for which part of the design

6) Results L147-149: This is repeating the methods under results section. Please revise to reduce on the wording.

7) Was smear microscopy using ZN or fluorescent Microscopy? please clarify

8) L166-167: The sensitivity for DST using phenotypic DST as reference had few samples, why not use agreement instead of sensitivity since this has less power as depicted by the wider confidence intervals. Alternatively compare agreement for DST between TrueNAT and GeneXpert and use phenotypic DST as a tie-breaker.

9) please review the PPV for MTB plus vs Microscopy: I get 53.5% instead of 42.4%

10) MTB plus vs Culture and MTB-RIF Vs pDST has been done before, what is new that this data is providing? This manuscript is focused on Mtbplus vs Xpert which should be the main focus. The same with Table 3.

11) Errors and invalids should indicate that it is comparing MTBplus and Xpert in the sub title

12) L201-202: please report in terms of the reduction in invalid results

13) The Rif indeterminate for TRACE call under Xpert, is expected as per the technology, why not present it separate without comparison? Compare Inditerminate and errors for RIF between platforms without TRACE call results.

14) Table 4 (which is referred as Table 3): MTB invalid, indeterminate and RIF indeterminate, ALL contribute to cost and must be discussed. They also require repeat testing and should be discussed under cost and feasibility section.

Reviewer #2:  This is an automated report for PONE-D-26-00956. This report was solicited by the PLOS One editorial team and provided by ScreenIT.

ScreenIT is an independent group of scientists developing automated tools that analyze academic papers. A set of automated tools screened your submitted manuscript and provided the report below. Each tool was created by your academic colleagues with the goal of helping authors. The tools look for factors that are important for transparency, rigor and reproducibility, and we hope that the report might help you to improve reporting in your manuscript. Within the report you will find links to more information about the items that the tools check. These links include helpful papers, websites, or videos that explain why the item is important. While our screening tools aim to improve and maintain quality standards they may, on occasion, miss nuances specific to your study type or flag something incorrectly. Each tool has limitations that are described on the ScreenIT website. The tools screen the main file for the paper; they are not able to screen supplements stored in separate files. Please note that the Academic Editor had access to these comments while making a decision on your manuscript. The Academic Editor may ask that issues flagged in this report be addressed. If you would like to provide feedback on the ScreenIT tool, please email the team at ScreenIt@bih-charite.de. If you have questions or concerns about the review process, please contact the PLOS One office at plosone@plos.org.

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Reviewer #1: Yes:  Willy Ssengooba

Reviewer #2: No

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Attachments

Attachment

Submitted filename: report_10.64898+2026.01.19.26344389.pdf

Diagnostic accuracy, operational feasibility, and cost considerations of Truenat MTB Plus and Xpert MTB/RIF Ultra for pulmonary tuberculosis

PONE-D-26-00956R1

Dear Dr. Zeeshan Sidiq,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Dr. Minal. Dakhave

Academic Editor

PLOS One