Leptospirosis Seroprevalence and Exposure Factors in Informal Settlements of French Guiana: an Opportunistic Survey

PLOS Neglected Tropical Diseases

Dear Dr. Le Turnier,

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Joseph M. Vinetz

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

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Additional Editor Comments:

There are important limitations of this study that simply must be addressed in a revision. It is recognized that such studies are very hard to do in the resource limited setting. However, the limitations here are important, and the lack of systematic sampling must be addressed.  

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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 of the study are clearly articulated, the design is appropriate, population well described,

Reviewer #2: Abstract : In the abstract, it is difficult to understand the difference between the primary study and the ancillary study. It may not be necessary to specify this in the abstract.

Introduction : Line 92 and following : Here you assert the link between leptospirosis and poverty in French Guiana, but that is the research question of your work. I would be more cautious in assumptions here.

Line 129 : A map showing the location of these cases and the neighborhoods where the study was conducted, if possible with a representation of informal settlement areas, would be useful.

Line 153 : aide ?

Reviewer #3: 1. Line 132: Please provide an overview of the original survey’s sampling methods rather than referring only to a prior publication. It is not possible to assess the implications of the results without additional sampling details.

2. Line 129: Clarify the number of informal settlements sampled. Based on the text (“Three areas near Cayenne were selected for on-site investigations: Boutilier [Remire-Montjoly] and PK13 and PK16 [Macouria]”), it appears that three areas within two informal settlements were included—please confirm.

3. Please summarize, in brief, the variables included in the cumulative exposure score to provide a general understanding of what factors were considered.

4. Clarify the languages used for survey administration (e.g., French only, or also Haitian Creole or others).

5. Line 159: The following statement needs clarification: “It was initially anticipated to use a threshold of 1:50 for positivity threshold. However, many sera were contaminated and the MAT results were too complicated to interpret with this threshold.”

Please elaborate on how contamination influenced interpretability and the rationale for raising the threshold to 1:100.

6. Line 106: Clarify the population to which the study objective refers in the statement:

“The primary objective of the study was therefore to assess the prevalence of prior Leptospira exposure in the population.”

Presumably this refers to residents of the three informal settlements, but this should be stated explicitly.

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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: Yes, Yes

Reviewer #2: It may be useful to specify that missing data were not considered in the calculation of odds ratios and p-values.

Reviewer #3: 1. Table 2: The reported N is 266, but the leptospirosis-specific questionnaire appears to have been administered to only 190 participants. Please clarify the denominator used for this table.

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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: Yes, Yes, Yes

Reviewer #2: Discussion:

Given the context of exposure widely shared by residents of these neighbourhoods, it would be interesting to supplement this study with seroepidemiological studies in nearby neighbourhoods with permanent housing.

Line 293 : It might be useful to specify whether these seroprevalence studies were conducted in response to the occurrence of cases.

As the population is Haitian and may have been exposed in their country of origin and in transit countries (Suriname in particular), it would be interesting to discuss this and cite any references in these countries.

Conclusion :

One cannot say that 7.5% is low; I would weigh it up.

Reviewer #3: The discussion should explicitly acknowledge or expand on the implication of the following limitations:

- Non-representative (convenience) sampling design

- High number of exclusions and/or missing data

- Limited capacity to generalize findings beyond the sampled communities

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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: The manuscript could benefit from some editing . A few examples are given below.

Material and Methods

Line 113-115: Health mediators helped the investigator and the participants when necessary during the on-field survey.

Please better specify the nature of ‘help’ provided. Did you mean to say: Health mediators assisted participants in filling out the questionnaire when necessary.

Discussion

Line 304-305: Because of a different titer threshold comparison was limited.

Consider: Since a different titer threshold was used, comparison may be questionable.

Line 342-343: Additionally, the time and place of acquisition of the previous exposure to leptospirosis cannot be ascertained since MAT remains positive for a long time.

Consider replacing ‘for a long time’ by ‘for several years’.

Reviewer #2: (No Response)

Reviewer #3: (No Response)

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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: The manuscript is adequate. The subject does not importantly add to novelty in science, but is OK. It is well written. My comments on editing are included in the section above.

Reviewer #2: Thank you for the opportunity to review this manuscript. The article deals with an important topic in a geographical region where it has been little studied and provides original findings that improve our knowledge and are likely to have practical implications. In particular, the estimation of seroprevalence in these understudied informal settlements and the identification of walking barefoot on wet ground as a risk factor for exposure are important findings that can be used for prevention purposes. Overall, the article is well written, based on a clear and high-quality methodology, and fits well with the journal's themes.

Reviewer #3: 1. General Overview

The authors report on Leptospira seropositivity, assessed by microscopic agglutination test (MAT) using a 17-serogroup panel, among what appears to be a convenience sample of 190 individuals from three informal settlements surrounding Cayenne, the capital of French Guiana, in 2022. The original serological sampling and survey tools were designed for a hantavirus investigation following an apparent increase in cases in preceding years. The present study repurposes those samples and metadata, supplemented with a leptospirosis-specific questionnaire administered to the same participants. The principal finding is a leptospirosis seroprevalence of 7.5% (95% CI: 4.7–11.4) using a ≥1:100 MAT threshold—lower than anticipated given the multiple exposure risks associated with informal settlement living conditions.

2. Major Comments

Representativeness and Generalizability: While I commend the authors for deriving additional insights from existing samples, the non-systematic nature of participant selection raises major concerns about the representativeness of the data. Given the low observed seroprevalence, even small changes in case numbers could substantially alter the prevalence estimate.

Public Health Relevance: It remains unclear how the current findings can meaningfully inform public health policy or programming, given the convenience sampling design and limited external validity. The authors should clarify what practical insights—if any—can be reasonably drawn from these results.

3. Additional Comments

Title: Please specify that the study was conducted in three informal settlements. The current title implies coverage of all informal settlements nationally. A clearer version might read:

Leptospirosis Seroprevalence and Exposure Factors in Three Informal Settlements of French Guiana: An Opportunistic Survey.

Line 93: The following sentence requires elaboration to better delineate how leptospirosis disproportionately affects vulnerable populations: “A third of affected individuals lacked health insurance and a third lived in informal settlements indicating that leptospirosis disproportionately affects vulnerable populations.” I'm a little confused by the logic of this sentence. Can the authors explicitly clarify how A (A third of affected individuals lacked health insurance) and B ( third lived in informal settlements) lead to C (leptospirosis disproportionately affects vulnerable populations)

Data availability: The current Data Availability statement appears internally inconsistent. Lines 394–395 state that data cannot be shared due to “ethical and legal restrictions,” yet lines 398–401 indicate that access to de-identified data may be granted upon reasonable request following approval from Santé Publique France and CNIL authorization. Further, the Data Availability section indicates that de-identified data can be accessed only after multiple institutional and CNIL approvals. Given that CNIL authorization governs identifiable data but does not restrict the sharing of fully anonymized datasets, it is unclear why the data cannot be made openly available in de-identified form. I encourage the authors to clarify whether these restrictions are institutional policy rather than legal requirement, and to consider providing an openly accessible anonymized dataset in alignment with PLOS NTD’s data-sharing standards.

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Reviewer #1: No

Reviewer #2: Yes:  Nicolas Vignier

Reviewer #3: No

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Dear Dr. Le Turnier,

We are pleased to inform you that your manuscript 'Leptospirosis Seroprevalence and Exposure Factors in Three Informal Settlements of French Guiana: an Opportunistic Survey' has been provisionally accepted for publication in PLOS Neglected Tropical Diseases.

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

Best regards,

Joseph M. Vinetz

Section Editor

PLOS Neglected Tropical Diseases

Joseph Vinetz

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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