PONE-D-20-06815

Active TB case finding in a high burden setting; comparison of community and facility-based strategies in Lusaka, Zambia

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: Yes

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

Reviewer #1: N/A

Reviewer #2: No

Reviewer #3: Yes

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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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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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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: Active case finding for tuberculosis (TB) is recommended by the World Health Organization as an approach to find particularly in high-burden settings, that why that manuscript is so relevant for the control of TB in development world.

Line 107 - History of cough, fever, night sweats, weight loss, chest pain and loss of appetite was documented for all patients presenting for TB screening;

The authors should clarify if all the TB symptoms screening were used based WHO's recommended.

The authors should explain how the diagnostic testing followed the standard of care for TB diagnosis in Lusaka. How were all sputum samples dropped off in study clinics and transported to the laboratory or clinic that have a facility like Xpert MTB/RIF testing.

In data analysis, the authors should be expanded and clarified to ensure that readers understand exactly what the researchers studied. Alternatively, they could include another statistical method as Poisson regression to fit the different variables. So that, the tables will be easier to understand.

Reviewer #2: I congrautulate the authors on conducting this piece of work. Indeed any extra-case detected is a couple of leaves saved from

exposure. The authors have carried out an implementation study whose objective appears to be, demonstrating the utility of

internvensions to improve active case finding at the facility and community. However i find it rather difficult to make out

what the actual intervention is, in other words there is need for clarity on what it is that is being done.

On first reading the study appears to have used a massive sample size but actually the samples that end up being tested to

confirm TB are only about 15-16%, this is because, the data has been filtered through a number of steps and it make it hard to figure out what the denominator is, surely the denominator ought to be with samples tested and the conclusions restricted to tested samples.

The extrapolation would be acceptable if the samples that get tested were randomly selected but this is not the case here. So the interpretation here my be somewhat misleading.

Abstract

The abstract is well written but the results reporting could benefit from clarifying the denominators

of each of the proportions reported and these out to be restricted to the samples tested. Only then will

it be possible to assess if the conclusions are appropriate for the results.

Introduction

Line 51, the authors state that 24,929 cases are missed in Zambia, this predominantly occurs in

In peri urban setting and that 50% missed at facilities. Can they expand on why 50% are missed at

facilities, is it a methodological?, awareness?, capacity problem? Ultimately this is what

the study aims to narrow ....as a gap!!

The introduction in general lacks the context within which the study is set, how do i evaluate the

intervention, who has used this interventions in the way you have designed it?, what does WHO recommend,

Zambia's TB incidence is ~ 208 per 100,000 persons per year, So, comparatively how is this approach expected to improve ACF relative to where it has been implemented?... will you approach improve time to identification, cost of extra case identified, or raw numbers of identified?... what is your measure of improvement.. With such a triangulation of information, one could fully understand what you are doing, how it compares elsewhere in terms of benefits and the anticipated improvements in ACF at detection level and cost involved...

Study setting and study population

There is limited information about the study site and population. For example one can not make out

the geographic distribution of the population used in your study, this is critical information as

the prevalence of TB by such sub-locations is likely to be known, it helps one evaluate the appropriateness of the

communities to include and the depth of the followup all of which determine how the scarce resources are apportioned.

Data collection and data management

What is the data availability policy to enhance the provenance of this?

Data analysis

The authors have not explained the statistical methods used, so it makes it hard to understand what analysis was done.

In my opinion there has been limited statistical input to the work

with the samples size used, a number of approaches could have been used to robustly analyse the data

The authors use the work Impact on case finding?, how is impact defined, raw numbers, proportion, cost per sample found?,

lives potentially save frome exposure

I see tables cited in materials and methods, to me this would mean results are being reported in MM

Results

It is shame, with this amount of data, alot of statistical analysis to properly unpick these characteristics

There samples are selected through a number of non-random selection criteria which makes extrapolations difficult

We need to be sure of the denominators used. From your selection procedure, you screened ~ 50%/50% the community and hospital

and the positive cases 91.5% and 8.5%, could you give an idea of what it costs to identify these (0.08*8,348).... actually the denominator should be the

the samples tested. Actually it appears the prevalence is 14.3% among tested at the facility and 3.6 in the community

What is the utility of p-values on line 187, in this case?? are you detecting more than you would expect?

I suspect the best use of this would be to establish that the ACF with and without any in intervention was significantly different

i.e. Q3 2016, Q3 2017... that is hwre the statistical differences would carry more weight!!

On line 194 you introduce, incidence at national level, is this published or is it data that comes from the your database. How can

that be independently verified, or is this peer reviewed data

It would be better if table 4 showed temporal gain rather than a compounded cumulative change

Discussion

I am unsure what the proportions represent, (in reference to the query raised on the denominator),

it makes it rather hard to follow the discussion

Reviewer #3: The very important topic needs only a punctual review to be published. the conclusions could be further elaborated to guide health systems in Africa.the objectives must be clear, the methodology described and the discussion of results must be aligned with the results presented

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Osvaldo Frederico Inlamea

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Attachments

Attachment

Submitted filename: PONE-D-20-06815.pdf

Active TB case finding in a high burden setting; comparison of community and facility-based strategies in Lusaka, Zambia

PONE-D-20-06815R1

Dear Dr.Kagujje,

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,

Frederick Quinn

Academic Editor

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: (No Response)

Reviewer #2: 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

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

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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: Yes

Reviewer #2: Yes

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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

Reviewer #2: Yes

**********

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: The authors have clarified the doubts in the first review.Targeting should be applied in TB interventions to improve yield and use resources more efficiently in Lusaka, Zambia.A screening tool should be provided for vulnerable populations to guide health workers to identify presumptive cases.

The authors used a representative number of individuals to screen TB in the community. Data improvement for TB, specifically synchronizing laboratory and TB registers, is another timely recommendation, especially in the current context of TB in Lusaka.

Reviewer #2: The paper is reporting findings from an implementation study, while i think a more robust statistical analysis could be done, i accept that the authors statement that they have another paper in preparation that would capture that. Therefore this would be considered a descriptive paper.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: Adrian Muwonge