Prevalence of Shigellosis among household contacts of index cases in the EFGH catchment area, Dhaka, Bangladesh

PLOS Neglected Tropical Diseases

Dear Dr. Qadri,

Thank you for submitting your manuscript to PLOS Neglected Tropical Diseases. After careful consideration, we feel that it has merit but does not fully meet PLOS Neglected Tropical Diseases'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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We look forward to receiving your revised manuscript.

Kind regards,

Nicholas J Mantis

Academic Editor

PLOS Neglected Tropical Diseases

Stuart Blacksell

Section Editor

PLOS Neglected Tropical Diseases

Shaden Kamhawi

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-4304-636XX

Paul Brindley

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-1765-0002

Additional Editor Comments:

There was a split decision between the two reviewers about the merit of the manuscript. While both Reviewers recognize the significance of the study, Reviewer 1 raised concerns about the analysis conducted to define relationships between the index cases and the household cases. The reviewer suggested you re-analyze and re-write the paper from the data set, but with more consideration of the types of analysis needed. This comment in particular influenced the decision for a major revision.

Journal Requirements:

1) Please ensure that the CRediT author contributions listed for every co-author are completed accurately and in full.

At this stage, the following Authors/Authors require contributions: Md Taufiqul Islam, Farhana Khanam, Md Nazmul Hasan Rajib, Md Ismail Hossen, Syed Qudrat-E-Khuda, Mahzabeen Ireen, Md Golam Firoj, Faisal Ahmmed, Prasanta Kumar Biswas, Amirul Islam Bhuiyan, S.M. Azadul Alam Raz, Md. Parvej Mosharraf, Md Taufiqur Rahman Bhuiyan, and Firdausi Qadri. Please ensure that the full contributions of each author are acknowledged in the "Add/Edit/Remove Authors" section of our submission form.

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Reviewers' Comments:

Reviewer's Responses to Questions

Key Review Criteria Required for Acceptance?

As you describe the new analyses required for acceptance, please consider the following:

Methods

-Are the objectives of the study clearly articulated with a clear testable hypothesis stated?

-Is the study design appropriate to address the stated objectives?

-Is the population clearly described and appropriate for the hypothesis being tested?

-Is the sample size sufficient to ensure adequate power to address the hypothesis being tested?

-Were correct statistical analysis used to support conclusions?

-Are there concerns about ethical or regulatory requirements being met?

Reviewer #1: The objectives are clear - that is to carry out a family study of shigellosis. However, there is no testable hypothesis. The population could be better described by age, sex, season.

Reviewer #2: The methods are clearly described and are appropriate for addressing the objectives of this study.

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Results

-Does the analysis presented match the analysis plan?

-Are the results clearly and completely presented?

-Are the figures (Tables, Images) of sufficient quality for clarity?

Reviewer #1: The analysis presented match the plan, however, the analysis could have gone into more depth and detail.

i felt the figures 2 and 4 are not needed.

Reviewer #2: The results match the analysis plan and are supported by the data presented. The tables and figures are clear and helpfully illustrate the key findings.

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Conclusions

-Are the conclusions supported by the data presented?

-Are the limitations of analysis clearly described?

-Do the authors discuss how these data can be helpful to advance our understanding of the topic under study?

-Is public health relevance addressed?

Reviewer #1: The authors found many shigella infections in household members of index patients, but it is difficult to know what this means.

Reviewer #2: The conclusions are clearly presented and are well-supported by the data provided.

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Editorial and Data Presentation Modifications?

Use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity. If the only modifications needed are minor and/or editorial, you may wish to recommend “Minor Revision” or “Accept”.

Reviewer #1: Editorial comments (the numbers refer to the line numbers).

37, Why mention vaccinations in the abstract when there are no licensed vaccines

83. Is there validation that a cold temp is needed. Could it be even harmful to maintain survival of shigellae?

85 stool specimens (plural) were…

92 reference(s) needed for the AST assays

98 is this the first time this customized card was used ? is this the same assay as used in the GEMs studies

114 “All HH stools positive for Shigella were not of the same species or serotype.” This sentence needs to ber explained. Not the same as what?

163 Explain “secondary education.” How many years of schooling is this?

189 I believe the ERC number should be included.

Reviewer #2: Minor comments/typographical:

Ln 37- I would favor replacing "vaccination" with " prevention" as the paper does not deal at all with vaccination and other prevention strategies are alluded to in the results (i.e reheating meals)

Ln 136- fill in the % value

Ln 186- Ethical clearance should go under methods

Fig 1- "CONSORT" should be capitalized

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Summary and General Comments

Use this section to provide overall comments, discuss strengths/weaknesses of the study, novelty, significance, general execution and scholarship. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. If requesting major revision, please articulate the new experiments that are needed.

Reviewer #1: This is an ambitious study to study shigella infections in households of index patients with shigellosis. It is an interesting study, but it seems the analysis could have gone into more depth in their analysis. For example:

1. When the study on household infections was being considered, did the authors have a hypothesis about the household infections? For example, did they want to determine if the infections were being spread between family members and if so, how? To answer this question, they would need to track the specific strains between household members. Perhaps alternatively, they just wanted to see if index cases identified households that have a high risk for shigellosis in general because of poor water/sanitation. If there was a hypothesis, what was the conclusion after doing the study?

2. What were the characteristics of the index cases? Did they all have dysentery or did some have watery diarrhea and were classified as an index case only after a positive culture was detected. Did the clinical symptoms change the rate of infections in household members?

3. What were the species and serotypes of the index cases, and how did these match the species / serotype of the infections in the household members. It would seem, there were many different strains of shigella in the household members, but they may not be related to the infection in the index cases.

4. What is the rate of shigella infection in the community? In this slum area of the city, it may be that shigella infections are common in the general population, especially infections that can be detected by PCR. Without a comparison of rates in a control group, it is difficult to know if the households had a higher rate than would be expected.

5. The analysis of households should be by household as well as individual. How many of the households had an infection. What was the distribution of the numbers of infections in the infected households. Did some households have many people infected and others had 0 or 1? It was not clear if the risk factors looked at households or only at individuals with infections.

6. I believe Table 1 can better describe the characteristics of the household members by age and sex.

7. Was there any seasonality among the index cases.

8. I believe the discussion section could be improved by first describing what the authors found in their study. I prefer to understand all the findings from this study first. Then, in later paragraphs compare their findings to other studies.

9. In terms of limitations, I would highlight the lack of control group. Ideally this could have been a case control study in which households of index patients with a non-diarrheal illness could be compared. Obviously, it is too late to do this now, but is there another way to estimate the rates in the community?

10. The antibiotic sensitivity patterns must have differed by species and serotype. By lumping together, I believe we do not have an appreciation of the true antibiotic sensitivity patterns.

Figure 2. I do not think a figure is needed. A table would be better.

Figure 3. Include the number of isolates tested

Figure 4. The figure does not have a label for the y axis. With so few pathogens identified with the Taq card, it would seem this does not deserve a figure. The data could be included in the text.

Reviewer #2: This manuscript describes a study assessing factors associated with Shigella carriage among household contacts of index children aged 6-35 months presenting with Shigella infection in Dhaka, Bangladesh. The cohort was relatively large, but still of limited size to detect differences in some factors. The methods were rigorously defined and support the conclusions drawn, which showed frequent asymptomatic carriage in household contacts and risk factors that included failure to reheat meals. I admit to being a little confused about how toilet type is shown to be significant in even the univariate analysis despite having only 1 infection in a total 2 individuals without flush toilets.

I think this paper does add to the general knowledge of household transmission of shigella and could be useful in developing strategies for screening or prevention.

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Reviewer #1: No

Reviewer #2: No

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Reproducibility:

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Dear Dr. Qadri,

We are pleased to inform you that your manuscript 'Prevalence of Shigellosis among household contacts of index cases in the EFGH catchment area, Dhaka, Bangladesh' has been provisionally accepted for publication in PLOS Neglected Tropical Diseases.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.

Should you, your institution's press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS.

Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Neglected Tropical Diseases.

Best regards,

Nicholas J Mantis

Academic Editor

PLOS Neglected Tropical Diseases

Stuart Blacksell

Section Editor

PLOS Neglected Tropical Diseases

Shaden Kamhawi

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-4304-636XX

Paul Brindley

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-1765-0002

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Reviewer's Responses to Questions

Key Review Criteria Required for Acceptance?

As you describe the new analyses required for acceptance, please consider the following:

Methods

-Are the objectives of the study clearly articulated with a clear testable hypothesis stated?

-Is the study design appropriate to address the stated objectives?

-Is the population clearly described and appropriate for the hypothesis being tested?

-Is the sample size sufficient to ensure adequate power to address the hypothesis being tested?

-Were correct statistical analysis used to support conclusions?

-Are there concerns about ethical or regulatory requirements being met?

Reviewer #1: yes, the objectives are clear

**********

Results

-Does the analysis presented match the analysis plan?

-Are the results clearly and completely presented?

-Are the figures (Tables, Images) of sufficient quality for clarity?

Reviewer #1: Yes

**********

Conclusions

-Are the conclusions supported by the data presented?

-Are the limitations of analysis clearly described?

-Do the authors discuss how these data can be helpful to advance our understanding of the topic under study?

-Is public health relevance addressed?

Reviewer #1: Yes

**********

Editorial and Data Presentation Modifications?

Use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity. If the only modifications needed are minor and/or editorial, you may wish to recommend “Minor Revision” or “Accept”.

Reviewer #1: Figure legend is run-on with the Table 1

Table 2 has a wording problem in one field: "number of persons live per room"

I thought one weakness would be mentioned: no community control group to know the rate of shigella positives in the general population.

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Summary and General Comments

Use this section to provide overall comments, discuss strengths/weaknesses of the study, novelty, significance, general execution and scholarship. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. If requesting major revision, please articulate the new experiments that are needed.

Reviewer #1: This is much improved and the authors have addressed the concerns from my earlier review.

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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.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

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