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. 2020 Mar 24;14(3):e0008193. doi: 10.1371/journal.pntd.0008193

ZIKA Virus infection in pregnant women in French Guiana: More precarious-more at risk

Edouard Hallet 1, Claude Flamand 2, Dominique Rousset 3, Timothée Bonifay 1, Camille Fritzell 2, Séverine Matheus 3, Maryvonne Dueymes 4, Balthazar Ntab 5, Mathieu Nacher 1,6,*
Editor: William B Messer7
PMCID: PMC7122809  PMID: 32208419

Abstract

Background

A recent study in French Guiana suggested that populations living in precarious neighborhoods were more at risk for Chikungunya CHIKV than those living in more privileged areas. The objective of the present study was to test the hypothesis that Zika virus (ZIKV) infection was more frequent in precarious pregnant women than in non-precarious pregnant women, as reflected by their health insurance status.

Methods

A multicentric cross-sectional study was conducted in Cayenne hospital including ZIKV pregnant women with serological or molecular proof of ZIKV during their pregnancy between January and December 2016. Health insurance information was recorded at delivery, which allowed separating women in: undocumented foreigners, precarious but with residence permit, and non-precarious.

Results

A total of 6654 women were included. Among them 1509 (22,7%) had confirmed ZIKV infection. Most women were precarious (2275/3439) but the proportion of precarious women was significantly greater in ZIKV-confirmed 728/906 (80.4%) than the ZIKV-negatives 1747/2533 (69.0%), p<0.0001. There were 1142 women classified as non-precarious, 1671 were precarious legal residents, and 1435 were precarious and undocumented. Precariousness and undocumented status were associated with a higher prevalence of ZIKV during pregnancy (adjusted prevalence ratio = 1.59 (95%CI = 1.29–1.97), p<0.0001), (adjusted prevalence ratio = 1.5 (95%CI = 1.2–1.8), p<0.0001), respectively.

Conclusions

These results illustrate that in French Guiana ZIKV transmission disproportionately affected the socially vulnerable pregnant women, presumably because of poorer housing conditions, and lack of vector control measures in poor neighborhoods.

Author summary

A recent study in French Guiana suggested that populations living in precarious neighborhoods were more at risk for chikungunya CHIKV than those living in more privileged areas. The objective of the present study was to test the hypothesis that Zika virus (ZIKV) infection was more frequent in precarious pregnant women than in non-precarious pregnant women as reflected by their health insurance status. A multicenter cross-sectional study was conducted including ZIKV pregnant women with serological or molecular proof of ZIKV during their pregnancy between January and December 2016. Health insurance information was recorded at delivery, which allowed separating women into: undocumented foreigners, precarious but with residence permit, and non-precarious. Overall 6654 women were included. Among them, 1509 (22,7%) had confirmed ZIKV infection. The majority of women were precarious, but the proportion of precarious women was significantly greater in ZIKV-confirmed 728/906 (80.4%) than the ZIKV-negatives 1747/2533 (69.0%). Precariousness and undocumented status were associated with a higher prevalence of ZIKV acquisition during pregnancy. The present results illustrate that in French Guiana, as elsewhere, ZIKV transmission disproportionately affected the socially vulnerable pregnant women, presumably because of poorer housing conditions, and lack of vector control measures in poor neighborhoods.

Introduction

French Guiana (FG) is a French overseas territory in South America. It has the highest Gross Domestic Product per capita in South America, and thus attracts numerous migrants in search of better economic opportunities. Women, and notably migrant women in FG, are especially concerned by inequity with low school enrolment, unemployment, teen pregnancies, and single parenthood [1]. The increase of vulnerable populations is a challenge for the health and social systems on a scale that is far greater in French Guiana than in mainland France[2]. In studies on health inequalities in French Guiana, being an immigrant is also associated with poverty, vulnerability and difficulties in accessing care leading to poor health outcomes.

Poor neighborhoods, with informal housing, lack of sanitation and presence of vector breeding places are especially suited for Aedes aegypti, the main vector for arboviruses in FG. This urban mosquito preferentially breeds around human dwellings, in outdoor water storage containers and in any recipient containing stagnant rain water. Densely populated areas with sustained human activity during the day are perfect for a daytime feeder that can bite several people in a short period of time [3].

The autochthonous transmission for the first chikunguya (CHIKV) outbreak in FG (2014), mainly affected foreign populations with precarious social status and those living in poor neighborhoods. In contrast, after further epidemics of dengue virus (DENV) in 2013, populations living in richer areas were mostly concerned. One hypothesis was that poor populations were more likely to have been immunized during previous DENV epidemics because of greater vector densities and transmission in these areas, whereas in rich neighborhoods populations were more likely to come from France and not be immunized thus being at risk for clinical disease[4].

The distribution of microcephaly in Brazil suggested a possible link between poverty and the risk of Zika virus -related microcephaly[5]. This epidemic spread to neighboring French Guiana in 2016, but until now there was no study of the impact of poverty on the prevalence of infection. In order to deal with the important proportion of asymptomatic Zika virus (ZIKV) infections [6] and a risk of delayed access to medical care in poor populations,[7,8] ZIKV serology was recommended at each trimester for all seronegative pregnant women. A first analysis of data collected during the 4 first months of the outbreak provided a representative picture of the spectrum of disease of ZIKV infection in pregnant women and mapped the intensity of the epidemic throughout French Guiana[6], however it did not look at specific subpopulations of pregnant women. However, the serological surveillance at each trimester during the ZIKV outbreak in 2016 allowed us to test whether the poorest pregnant women were more likely to acquire ZIKV than more socioeconomically privileged women. The objective of the study was thus to compare the prevalence of ZIKV contact in FG for pregnant women according to their health insurance status (HIS).

Materials and methods

A multicenter, cross-sectional study was conducted in Cayenne (CHAR), Kourou (CHK) and Saint Laurent (CHOG) hospital, the main cities and the main hospitals in FG.

Population

We included all deliveries, spontaneous abortions or pregnancy terminations for medical reasons between January 2016 and December 2016, 3 months after the official declaration of the end of the outbreak. Women without ZIKV serology were excluded. We also included women with positive RT-PCR even if they did not have any serology. Fig 1 shows the study flowchart. The STROBE checklist is indicated in S1 Checklist.

Fig 1. Study flowchart.

Fig 1

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Origin of patients and sample selection.

Data collection

The dataset was centralized by the national reference center for arboviruses (CNR arbovirus) at Pasteur institute in Cayenne. Data were collected by clinicians, pediatric nurses, or midwives in charge of pregnancy monitoring in the 3 hospital maternity wards. clinical, socio-demographic and geographical individual data were collected at enrolment and at each obstetrical consultation by interviewing the pregnant women. The following variables were available: age, area of residence, pregnancy trimester and pregnancy outcomes (type, date, attendant, place, and last menstruation date). Health insurance information was obtained from the hospital information systems (PMSI) of Cayenne and Saint Laurent du Maroni hospital, but not from Kourou hospital.

Health insurance status

For health insurance status, we distinguished between patients in a precarious social situation and those who were not. Patients without any health insurance[9], those benefiting from free universal health care called Protection Universelle Maladie (PUMa) (which allows access to health for legal residents who are not already covered usually associated with a complementary insurance the CMUc), or those benefiting from “state medical aid” or “AME” (government run insurance program specifically conceived for undocumented migrants who become eligible after 3 months of residency in a French territory) were considered to be in a precarious social situation. Indeed, the annual income of a single person should be less than 8653.16 € (a very low income for French Guiana) to benefit from the above health insurance regimens. Persons with regular social security were considered non precarious. Women seen in Kourou maternity had no health insurance information. Women without health insurance can receive free care (including ZIKV screening) at the hospital after receiving a “PASS” voucher from a hospital social worker, which allows covering all expenses.

Study area

We will subsequently refer to different town groupings: Western, savanas, central coastal, and Eastern. The main groups living in the western area are the Maroons, descendants of escaped slaves (15% of the total population of French Guiana) and Amerindians (3%) who live in the south west. Savannas include a mix of previous ethnicities and international workers for aerospace industries. The population of the Central Coastal area is marked by local ethnic groups including Creoles (60% of the total population), people of European ancestry (14%) who essentially come from mainland France and various immigrants from Brazil, Haiti, Caribbean islands, China and southern Asia. The eastern region includes a mix of creole and Amerindian populations.

Laboratory diagnosis

Serum and urine samples collected for RT-PCR analysis were obtained during trimestrial surveillance and during possible acute symptomatic illnesses, or in the presence of fetal death or fetal structural abnormalities. Placenta and amniotic liquid were assayed for ZIKV RNA by real time RT-PCR using the Lanciotti method[10], the RealStar ZIKV RT-PCR kit, or ELISA serology. Analyses were realized by the National Reference Center of Arboviruses of Pasteur Institute in French Guiana and by the Cayenne Hospital laboratory. Neutralization for IgG could not be implemented, therefore we excluded probable cases with negative IgM and positive IgG.

Statistical analyses

Bivariate analysis of categorical variables used Poisson regression to obtain prevalence ratios rather than odds ratios, which may overestimate the magnitude of association. Available variables were used in the multivariate analysis using modified Poisson regression in order to obtain prevalence ratios. Stata 12.0 was used for analysis (College Station, Texas, USA).

The retrospective use of anonymized data from patient records is authorized by French law. More specifically, in the emergency context of the Zika epidemic it was part of the health authorities’ epidemiologic surveillance research efforts aiming to better understand this emerging problem.

Results

A total of 6,654 pregnant women were eligible for the study between 01/2016 and 12/2016 as pregnant women in FG. Because of the absence of reply from the medical information department in Kourou, the 2,621 women (39%) with unknown health insurance mostly lived in Kourou (20%). For this study, 4,380 pregnant women were included with at least one sample and with available health insurance information reporting. The final population analyzed count 3,439 women, because 837/6654 women had positive IgG and negative IgM serology without immunocapture. Overall 16.5% of precarious women had positive IgG and negative IgM serology without immunocapture whereas 9.82% of women with normal health insurance had positive IgG and negative IgM serology without immunocapture, P<0.001.

The average age of the study population was 27.9 years-old (range 12–52 years). Overall, 2.1 samples/women were collected on average (range: 1–13), with an average time of 78 days± 53 days between two consecutive serologies for the 3,025 women with more than one sample. Women with a unique sample at the end of pregnancy were 1,168 (13.9%). Abortion represented 216 (3.7%) of the 5817 recorded pregnancy outcomes. The term at diagnosis was compiled for 2,968 (86.3%) women with an average term at sample of 28±10 weeks of amenorrhea (range: 2–42 WA). Regarding residence location: Central Coastal area (6 communes) represented 33.8% of the study population (1,163/3,439 births), Western French Guiana (8 communes), represented 62.4% of births (2145/3439), Eastern French Guiana (4 communes), 1.3% of births (45/3439), Savannas (4 communes), 1.3% of births (45/3439), and visitors, 1.2% (41/3439).

Table 1 shows the characteristics of precarious women: younger women, those from western French Guiana were more precarious (P<0.001), and precarious women seemed less likely to be diagnosed in the first trimester.

Table 1. Characteristics of the precarious and non-precarious women.

Precarious
No Yes Total
Residence location
Savanas 15 30 45
33.33 66.67 100.00
Western 405 1740 2145
18.88 81.12 100.00
Central Coastal 517 646 1163
44.45 55.55 100.00
Eastern 14 31 45
31.11 68.89 100.00
Age
<20 98 444 542
18.08 81.92 100.00
[20–30[ 430 1189 1619
26.56 73.44 100.00
0–40[ 393 740 1133
34.69 65.31 100.00
>40 43 101 144
29.86 70.14 100.00
Trimester at diagnosis
pre-fertilization 13 9 22
59.09 40.91 100.00
1st trimester 161 359 520
30.96 69.04 100.00
2nd trimester 245 683 928
26.40 73.60 100.00
3rd trimester 202 582 784
25.77 74.23 100.00
term 316 784 1100
28.73 71.27 100.00
post-conception 3 14 17
17.65 82.35 100.00
At least 1 positive IgM
123 562 685
17.96 82.04 100.00
At least 1 positive IgG
143 668 811
17.63 82.37 100.00
Positive PCR
38 45 83
45.78 54.22 100.00
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Among the pregnant women surveyed, 906 (26.3%) had been exposed to ZIKV. Most pregnant women were precarious 2475/3439. The proportion of precarious women was significantly greater in ZIKV confirmed 728/906 (80.4%) than the ZIKV negatives 1747/2533 (69.0%), p<0.0001. Among precarious, irregular immigrants seemed more exposed 97/300 (32.3%) than French nationals 361/ 1310 (27.6%) (p = 0.10).

Precariousness for legal residents (adjusted prevalence ratio APR = 1.37) and undocumented residents (AME: APR = 1.47 and no insurance: APR = 1.59) were associated with a significant increase of ZIKV prevalence adjusted for residence location (Table 2).

Table 2. Crude and adjusted prevalence ratios (Poisson regression) for ZIKV infection in pregnant women in French Guiana in 2016.

Confirmed ZIKV (n = 906) Negative ZIKV (n = 2533) PR (95% CI) p aPR(95% CI) p
Precariousness (N = 3439)
Not precarious 178 (18.5%) 786 (81.5%) - - - -
PUMa* 361 (27.6%) 949 (72.4%) 1.5 [1.3; 1.8] <0.0001 1.4 [1.1; 1.6] 0.001
AME** 270 (31.2%) 595 (68.8%) 1.7 [1.4; 2.0] <0.0001 1.5 [1.2; 1.8] <0.0001
No insurance 97 (32.3% ) 203 (67.7%) 1.8 [1.4; 2.2] <0.0001 1.6 [1.2; 2.0] <0.0001
Residence Localization (N = 3439)
Savannas 23 (51.1%) 22 (48.9%) 1.5 [1.3–1.8] <0.0001 2.7 [1.7–4.1] 0.008
Western 650 (30.3%) 1495 (69.7%) 1.5 [1.4–1.7] <0.0001 1.5 [1.3–1.8] <0.0001
Central Coastal 212 (18.2%) 951 (81.8%) _ _
Eastern 12 (26.7%) 33 (73.3%) 1.3 [1.0–1.7] 0.02 1.4 [0.8–2.5] 0.3
Visitors 9 (22.0%) 32 (78.1%) 1.6 [1.2–2.0] <0.0001 1.1 [0.6–2.2] 0.7
Age (years) -
<20 159(29.3) 383(70.7)
[20–30] 411(25.4) 1208(74.6) 0.8 [0.7–1.03] 0.12 0.9 [0.8–1.1] 0.6
[30–40] 294(25.9) 839(74.1) 0.9 [0.7–1.07] 0.21 1 [0.8–1.2] 0.8
>40 41(28.5) 103(71.5) 0.9 [0.7–1.3] 0.86 1.05 [0.7–1.5] 0.7
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Discussion

The present results show that the proportion of ZIKV-positive women was significantly greater in precarious women overall, and mostly in undocumented foreign women. Indeed, in the subgroup of precarious women, there was a trend suggesting greater exposure for undocumented women, presumably because they often live in shantytowns where vector proliferation and contact is greater than among documented precarious women who may have greater access to subsidized housing. Overall Western French Guiana was more affected than the rest of the territory[6]. The greater proportion of women with positive IgG and negative IgM serology without immunocapture whereas 9.82% of women with normal health insurance had positive IgG and negative IgM serology without immunocapture, P<0.00in the precarious group may also have reflected earlier infections during pregnancy, thus a proxy for greater risk.

Women living beyond the Coastal areas, where vector control is not as developed as in urban areas, were also significantly more likely to be infected by ZIKV.

The variables used are a coarse proxy for environmental and behavioral aspects linked to poverty, which were not measured. However they have been robustly associated with a number of chronic and acute health problems in French Guiana. [7,11]The present study was hospital-based and the exact health insurance status was not always recorded for different reasons: lack of time in a busy obstetrical ward, communication problems because of the very large number of women who do not speak French. Although, the type of health insurance is based on legal or illegal residence, length of stay, and on having an income below a certain threshold, it is conceivable that health insurance as a proxy for social precariousness is not perfect and that some women in the regular health insurance group may have been precarious. The limited number of adjustment variables, notably the living area used for the analysis did not allow to precisely study confounding between individual and collective socio-economic determinants. Despite these limitations, the present results were not a quest for any significant p value but were a clearly defined a priori hypothesis that was tested with the available data from the 2 biggest maternities in French Guiana, which capture most deliveries.

These results, previous observations on dengue and CHIKV, observations in patient with chronic diseases, in pregnant women, and in persons renouncing to health care all suggest that social inequalities of health often affect the same populations with poorer living conditions and reduced access to care and prevention.[4,12] The present results emphasize that population approaches for a range of selected problems may be more pertinent than an array of vertical social programs in different populations. Indeed, many community approaches are presently funded as thematic (HIV prevention and testing, addictions…) and community worker thus often only focus on a single theme hence missing opportunities to improve outcomes for other important health problems. Relationship between social aspects and seropositivity to ZIKV, to DENV (p<1012)[13], and to CHIKV (p<1015) [14] suggests a complex interplay between individual factors and ecological/environmental factors.[15] At the individual level, underprivileged populations often have lower levels of health literacy; they often live in shacks surrounded by mosquito-breeding grounds and little protection from vectors. At the ecological level, these individual situations add up, and in addition, these populations generally gather in informal habitats in areas that are more likely to have high vector densities, and to be less prioritized by municipal and regional services.[16] Further studies should aim precisely define the potential multilevel causal paths underpinning this statistical association: A better mapping of vector breeding sites in priority areas, specific knowledge attitudes and behavior studies in underprivileged populations, a survey of the geographic distribution of vector-control interventions, notably relative to underprivileged areas. Such data would allow devising interventions aiming at improving health literacy and empowering populations relative to the prevention of vector-borne diseases, and improving the reach of vector-control by specifically targeting such areas.

In conclusion, during the ZIKV epidemic in French Guiana, precarious pregnant women and women living in Western French Guiana were significantly more affected by ZIKV than non-precarious women and women living in Central coastal areas.

Supporting information

S1 Checklist. STROBE checklist.

(DOC)

Click here for additional data file. (94.5KB, doc)

Data Availability

In France, all computer data (including databases, in particular patient data) are protected by the National Commission on Informatics and Liberty (CNIL), the national data protection authority for France. CNIL is an independent French administrative regulatory body whose mission is to ensure that data privacy law is applied to the collection, storage, and use of personal data. As the database of this study was authorized by the CNIL, we cannot make available data without prior agreement of the CNIL. The data may be made available by the authors but according to French law, researchers wishing to obtain the data must obtain additional authorization with the CNIL. In practice, the first step for any researcher wishing to obtain the data should be to ask the Coordination Regionale de lutte contre le SIDA (corevih@ch-cayenne.fr) who will guide the researcher through the process with the CNIL.

Funding Statement

The authors received no specific funding for this work.

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PLoS Negl Trop Dis. doi: 10.1371/journal.pntd.0008193.r001

Decision Letter 0

Scott B Halstead, William B Messer

28 Jan 2020

Dear Pr. Nacher,

Thank you very much for submitting your manuscript "ZIKV infection in pregnant women in French Guiana: more precarious-more at risk." for consideration at PLOS Neglected Tropical Diseases. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. In light of the reviews (below this email), we would like to invite the resubmission of a significantly-revised version that takes into account the reviewers' comments.

Overall the reviews were favorable, however, we cannot make any decision about publication until we have seen the revised manuscript and your response to the reviewers' comments. Your revised manuscript is also likely to be sent to reviewers for further evaluation.

When you are ready to resubmit, please upload the following:

[1] A letter containing a detailed list of your responses to the review comments and a description of the changes you have made in the manuscript. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

[2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file).

Important additional instructions are given below your reviewer comments.

Please prepare and submit your revised manuscript within 60 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email. Please note that revised manuscripts received after the 60-day due date may require evaluation and peer review similar to newly submitted manuscripts.

Thank you again for your submission. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments.

Sincerely,

William B Messer

Associate Editor

PLOS Neglected Tropical Diseases

Scott Halstead

Deputy Editor

PLOS Neglected Tropical Diseases

***********************

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 clear. The study design and the population have to be more precisely detailed. The sample size is large. Analysis is correct but lack go adjustment. No concern about ethical or regulatory requirements.

Reviewer #2: The objectives of this study are clearly stated in the the hypothesis "that in pregnant women Zika Virus (ZIKV) was more frequent in precarious women than in non-precarious women as reflected by their health insurance status". The analytic approach supports the aims of the hypothesis.

However, the stated study design of "a retrospective case-control" is incorrect in reference to the study sample and analytic approach. The sample of of "all deliveries or medical abortions between January 2016 and December 2016" and the use of prevalence ratios suggest that a "cross-sectional study design" better describes this work. The sample was taken from a singular point in time. The authors then estimate the association between disease prevalence (ZIKV serology) and other prevalent health factors (precariousness via health insurance status) at that point in time. All of which is suggestion of a cross sectional study, not a case control.

Reviewer #3: How can we be sure that woment with regular health insurance are not precarious?

The reason why neutralization for IgG could not be implemented should be explained.

Why is there no mention of an ethical committee for this study?

--------------------

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: Analysis match the analysis plan but the results have to be completed to be comprehensive.

Reviewer #2: Overall, the analysis is clearly presented and the paper proceeds in a logical manner. However, the measure of association in the body of the paper, adjusted prevalence ratio (APR) does not match the measure in abstract (adjusted odds ratio, aOR). Please change the measure and language in the abstract (AOR, "associated with a higher risk of ZIKV") to match the body of the text (APR, "associated with a significant increase of ZIKV prevalence").

Reviewer #3: We need to understand who are the 837/6654 women who had positive IgG and negative IgM serology without immunocapture. It could represent a biais for the final analysis.

The 2,621 women (39%) with unknown health insurance lived principally in Kourou

municipality (20%). This is a high rate, the risk that a high number of these women are precarious should be discussed.

For abortion, please specify if there are spontaneous or not.

It is stated that among precarious, irregular immigrants seemed more exposed 97/300 (32.3%) than French nationals 361/ 1310 (27.6%) (p=0.10). It need to be discussed further.

--------------------

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 conclusions are supported by the data. Limitations are clearly described but could be discussed further.

Reviewer #2: The conclusions are robust and link well to public health relevance in the context of the ZIKV epidemic in French Guiana.

The second to last paragraph could benefit from some clarifications:

- What specific vertical social programs are less beneficial than which population health approaches, in the context of preventing/addressing infectious disease in French Guiana?

- For the interplay between the individual factors of precariousness/poverty and the ecological/environmental factors resulting in the outcome of ZIKV as well as DENV and CHIKV:

~What are potential hypotheses for the possible associations or pathways resulting infection?

~How could these be verified and by what experimental designs?

~How could these future studies be used to inform public health in a manner that would mitigate or prevent the next infectious outbreak, especially among a vulnerable/precarious/impoverished population?

Reviewer #3: The epidemiology and the repartion of ZIKV infection in FG should be discussed. We need to know where most of the cases occured in this territory.

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Editorial and Data Presentation Modifications?

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Reviewer #1: Add a table with description of women by study categories.

Reviewer #2: - Change the study design from case-control to cross-sectional.

- Change the measure of association in the abstract from AOR to APR, remove reference to the risk of ZIKV and add a reference to the prevalence of ZIKV.

- Clarify some of the language and phrasing in the discussion section.

Please refer to the suggested minor modifications in the above sections for more details.

Reviewer #3: There is no author listed with affiliation 4 Regional epidemiology unit of French Public Health Agency, Cayenne, French Guiana.

--------------------

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: General comments

This study addresses an important topic in an area where data are limited: Zika virus infection in pregnant women in a French oversea territory located in the Amazon area and its relation to social insecurity. The proportion of women affected by Zika infection is very high and women in precarious situations seem more often concerned.

Although the study is monocentric, the number of pregnant women included is large.

In view of the existence in France of health insurance coverage for the poor and the undocumented (Complémentaire Santé Solidaire -CSS- and Aide Médicale d’Etat – AME-), the status relating to health insurance is a good proxy for measuring precariousness. However, it could be useful to discuss the lack of more precise data on the social situation. In particular, how were people without health insurance coverage treated?

As the rights to CSS and AME run 12 months regardless of changes in administrative status, the social situation of people may be different than that announced (undocumented migrants, precarious and non-precarious French resident )

Specific comments for revision

Title:

Zika Virus should be written in full in the title

Abstract:

Avoid repetitions “Most pregnant women were precarious 2275/3439. Most women were precarious but…”

Please specify the number of women belonging to the 3 analysis categories (undocumented, precarious, non-precarious)

Avoid “as elsewhere,” in the conclusion.

In addition to the inequalities of vector control by neighborhoods, it would be interesting to question the differences in personal behavior in the application of these same measures

Manuscript:

Authors’ affiliations: an affiliation does not correspond to any author (4 Regional epidemiology unit of French Public Health Agency, Cayenne, French Guiana)

Detail abbreviations: GDP

Between the summary which speaks of a monocentric study and the results which speak of 3 sites, it is not clear who was included in this study

Corrected “assurance”.

There are inaccuracies to correct on French health insurance coverage

The Universal health coverage (=CMU) (basic health insurance coverage implemented in 1999) no longer exists since 2016, it was merged with national Health Insurance (Assurance maladie) during the Universal Health Protection reform (Protection universelle maladie -Puma-). In addition, the CMU does not have a 3-month residency obligation in France, unlike the AME.

The complementary universal health coverage (=CMUC) changed its name on 1/11/2019 when it was merged with Aid to complementary health (=ACS) and is now called complementary health solidarity (Complémentaire Santé Solidaire = CSS)

In addition, the CMU does not have a 3-month residency obligation in France, unlike the AME

Please specify for CSS and AME the resource criteria which explain why they can be used as a proxy for their social status

Prefer the term national Health Insurance (Assurance maladie) to that of social security (Sécurité Sociale) for others

The paragraph on the biological diagnosis must be reviewed and clarified

Avoid “ extraordinary context”

The methods of collecting data must be more precisely described. Likewise, it is not clear which motherhood participated and why.

A flow chart specifying the site for monitoring women and their health coverage would be welcome

If prevalence ratio from Poisson regression were used, why in the abstract we found Odds Ratio?

The procedures for diagnosing Zika infection should be described much more precisely:% of women diagnosed with PCR,% of women diagnosed with serology and in what term, with what result of the previous serology, etc. A detailed table would be welcome. These results will ideally be presented according to the 3 study categories

“and no insurance: APR = 1.59”? You did not specify before having included people without health insurance. What are they? Profile?

Table 1: detail the abbreviations at the bottom of the table. Specify the method of analysis in the title.

Why not have adjusted model on age? Other adjustment variables, if available, would be welcome. The model as it is is difficult to interpret.

Discussion:

Can you discuss further why vector control measures are less implemented in certain regions and the policy of the regional health agency on this point. In particular, a qualitative insight into the real situation in the districts concerned would be useful for understanding the results.

The discussion could be enriched with international references having investigated the relationships between arboviruses and social situation

Reviewer #2: This is an interesting analysis acceptable for publication following minor revisions. One minor thematic point relates on the authors comments on "The unusual distribution of mircocephaly in Brazil, suggested a possible link between poverty and the risk of ZIKV related microcephaly..." The association between poverty and increased risk of infectious disease should not be considered unusual. Especially given the authors prior notes concerning the lack of sanitation and presence of disease carring insects in poor neighborhoods in French Guiana.

Reviewer #3: This an interesting study that highlights the fact that precarious people are more at risk of Zika infection in French Guiana. We need to better understand the methodology and the recommandation for public Health.

--------------------

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Reviewer #2: No

Reviewer #3: No

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PLoS Negl Trop Dis. doi: 10.1371/journal.pntd.0008193.r003

Decision Letter 1

Scott B Halstead, William B Messer

27 Feb 2020

Dear Pr. Nacher,

Thank you very much for submitting your manuscript "ZIKA Virus infection in pregnant women in French Guiana: more precarious-more at risk." for consideration at PLOS Neglected Tropical Diseases. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. The reviewers appreciated the attention to an important topic. Based on the reviews, we are likely to accept this manuscript for publication, providing that you modify the manuscript according to the review recommendations.

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***********************

Please review the minor edits and one question from the Associate Editor in the uploaded version of the tracked-changes manuscript.

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To enhance the reproducibility of your results, PLOS recommends that you deposit laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see http://journals.plos.org/plosntds/s/submission-guidelines#loc-materials-and-methods

Attachment

Submitted filename: WBM_ZIKV precariousness manuscript_revision (1).docx

Click here for additional data file. (82.8KB, docx)
PLoS Negl Trop Dis. doi: 10.1371/journal.pntd.0008193.r005

Decision Letter 2

Scott B Halstead, William B Messer

3 Mar 2020

Dear Pr. Nacher,

We are pleased to inform you that your manuscript 'ZIKA Virus infection in pregnant women in French Guiana: more precarious-more at risk.' 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,

William B Messer

Associate Editor

PLOS Neglected Tropical Diseases

Scott Halstead

Deputy Editor

PLOS Neglected Tropical Diseases

***********************************************************

PLoS Negl Trop Dis. doi: 10.1371/journal.pntd.0008193.r006

Acceptance letter

Scott B Halstead, William B Messer

17 Mar 2020

Dear Pr. Nacher,

We are delighted to inform you that your manuscript, "ZIKA Virus infection in pregnant women in French Guiana: more precarious-more at risk.," has been formally accepted for publication in PLOS Neglected Tropical Diseases.

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PLOS Neglected Tropical Diseases

Shaden Kamhawi

Editor-in-Chief

PLOS Neglected Tropical Diseases

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Checklist. STROBE checklist.

    (DOC)

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    Attachment

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    Attachment

    Submitted filename: WBM_ZIKV precariousness manuscript_revision (1).docx

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    Attachment

    Submitted filename: Dear Editor.docx

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    Data Availability Statement

    In France, all computer data (including databases, in particular patient data) are protected by the National Commission on Informatics and Liberty (CNIL), the national data protection authority for France. CNIL is an independent French administrative regulatory body whose mission is to ensure that data privacy law is applied to the collection, storage, and use of personal data. As the database of this study was authorized by the CNIL, we cannot make available data without prior agreement of the CNIL. The data may be made available by the authors but according to French law, researchers wishing to obtain the data must obtain additional authorization with the CNIL. In practice, the first step for any researcher wishing to obtain the data should be to ask the Coordination Regionale de lutte contre le SIDA (corevih@ch-cayenne.fr) who will guide the researcher through the process with the CNIL.

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