PONE-D-21-00739

Remote analysis of Sputum Smears for Mycobacterium Tuberculosis Quantification using Digital Crowdsourcing

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

Reviewer #3: No

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

Reviewer #3: No

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Authors analyze the feasibility of a crowdsourced approach to tuberculosis image analysis that presents interesting results.

Although the crowdsourced approach nor the application in health problems are not new, the specific application is interesting and the obtained results suggest a possible use in tuberculosis diagnosis.

It is convenient to enhance the quality of the images.

The used methodology should be more descriptive.

Reviewer #2: Major comments:

The manuscript " Remote analysis of Sputum Smears for Mycobacterium Tuberculosis Quantification using Digital Crowdsourcing" reports the feasibility of a crowdsourced approach to sputum smear microscopic analysis for the diagnosis of tuberculosis. The authors investigated whether volunteers (game players) would be able to count acid-fast bacilli in digitized images of sputum smears with an online game. Against expert microscopists as gold standard, the F1 score, sensitivity and positive predictive of volunteers reached to 0.933, 0.968 and 0.916, respectively. In conclusion, the authors expected that their system, in which acid-fast bacilli (AFB) microscopic images obtained by a mobile phone were distributed through the mobile network, could be an effective tool as a remote diagnosis platform or an educational tool. They also believed that crowdsourced methodologies employed in this study could produce practical data for other diagnostic methods and development of artificial intelligence systems.

Technically, providing AFB smear images obtained by mobile phone to expert healthcare professionals in remote area could be a useful tool for high burden areas without adequate medical systems. It is also very important to show the diagnostic ability of non-professional volunteers could be comparable using a crowdsourced approach with well verified criteria. As authors mentioned, this approach could product constructive data for developing not only human intelligence but artificial intelligence systems.

As for TB diagnosis, methods processing thousands of AFB smear samples would not be practical. Basically, it is hard to obtain appropriate sputum sample, especially from children, extrapulmonary tuberculosis and disseminated TB. The latter two are often observed people living with HIV. Children and people living with HIV are the most vulnerable population to TB. Therefore, the World Health Organization calls for the development of a rapid and non-sputum tests capable of detecting TB at the point-of-care (POC), because sputum smear test has low diagnostic sensitivity in children, extrapulmonary TB, and people living with HIV.

Developing a system for resource-limited area, which is operated by a crowdsourced concept via mobile phone network, has various utilities not only for image diagnostic purposes but other fields. However, for reasons mentioned above, developing a system for AFB smear diagnosis would not efficiently contribute to the incremental diagnostic yield of TB.

Minor points

tp= Bacillus detected by at least Q out of SG players.

fp = Point, that is not a bacillus, voted by Q out of SG players.

fn= Bacillus that it is not “voted” by Q out of SG players.

No explanation for abbreviation “SG”. What is SG stand for?

Reviewer #3: Microscopy will continue to play a key role in diagnosis and and treatment monitoring of tuberculosis. Efforts to improve performance are lauded such as the work that is being presented here. However, they are several concerns.

Major

1. The authors have only reported precision ( F1 score), sensitivity and PPV. Use of F1 score is limited in that it does not take into account true negative ( specificity). It is advisable to use either Mathews correlation or Kappa statistic when assessing binary classifiers. The specificity should also be reported.

I would interested to see these analysis before making any decision on this submission

2.It is not immediately clear how crowdsourced tasks would be used in clear setting. Does it mean that reading of smears could in future be done through crowd sourced reading (gamification?)

Minor

1. The manuscript does not flow well . The first paragraph of results and discussion seems to seems to fit better under methodology

2. There are no line numbers which makes it difficult to pint out exact areas/ sentences where comment is directed

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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Remote analysis of Sputum Smears for Mycobacterium Tuberculosis Quantification using Digital Crowdsourcing

PONE-D-21-00739R1

Dear Dr. Ledesma-Carbayo,

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.

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PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: N/A

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: It seems to me that authors have fulfilled the reviewers' comments. The paper can be published in its current form.

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Reviewer #1: No