PONE-D-21-37124Scorpion envenomation in the state of São Paulo, Brazil: Spatiotemporal analysis of a growing public health problemPLOS ONE

Dear Dr. Lacerda,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’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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ACADEMIC EDITOR: Reviewers valued this contribution as it describes a relevant and interesting public health phenomenon, i.e., the increment in the incidence of scorpion stings and their derived envenomings in the state of Sao Paulo, Brazil. Reviewers also highlighted a number of issues that need to be taken into consideration when preparing a revised version of this manuscript. The most important aspects to consider are: (a) the need to make the data of the study publicly available, as per the policy of the journal, (b) the need to discuss the limitations of the methodology used andthe conclusions reached, and (c) the strengthening of the discussion by considering some aspects mentioned by the reviewers, such as the possible geographical differences within the state regarding incidence and mortality due to scorpion sting envenomings, and further exploring and discussing the hypothesis presented to explain the increment in the incidence of these accidents, among other points.  

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Academic Editor

PLOS ONE

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4.  The reviewers appreciated the relevance of this study, since it focuses on an important public health issue in the state of Sao Paulo, i.e., the drastic increment in the incidence of envenomings by scorpion stings, a phenomenon that deserves analysis and attention by the research community and the public health system of the state. Reviewers highlighted a number of issues that should be carefully considered and taken into consideration for preparing a revised version of the manuscript.

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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: Yes

Reviewer #2: I Don't Know

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: No

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: No

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: This study analyzed the historical series of scorpion stings in São Paulo, Brazil from 2008 to 2018 and occurrences in the 645 municipalities of this state.

Abstract:

1. "standardized by sex and age": change to "stratified by sex and age"

2. "the deaths were randomly distributed": randomly or proportional to incidence?

3. "Our findings that identify areas and populations at risk for scorpion envenomation and resulting fatalities can...": Change sentence. Suggestion: "In this study, we identified areas and population at risk for SE and associated-fatalities, which can..."

4. "...with these animals and avoid fatalities, especially in the most vulnerable population." Why mostly in the vulnerable population? Is it possible to conclude that from the results?

Introduction:

1. "Tityus is most medically relevant due to envenomations in children and high incidences in recent years." The other genera do not sting children? Strange sentence.

2. "Four species are epidemiologically important in Brazil: Tityus serrulatus, T. bahiensis, T. obscurus, and T. stigmurus." Sentence needs reference.

3. "Antivenin": Change to "antivenom" in the whole text.

4. "Antivenin is recommended for moderate and severe cases. [10, 13, 14]". Where? In Brazil? Accornding official guidelines?

5. "serious cases": change to "severe cases" in the whole text.

6. "at least minimize the sequelae and/or deaths". Sequelae? Which types?

7. "For this reason, it is extremely important 113 to characterize scorpion exposures in terms of victims as well as spatiotemporal factors." What 'in terms of victims' mean?

8. "This study consequently describes": Delete 'consequently'.

Methods

1. "scorpion exposures": change to "scorpion stings"in the whole text.

2. Include environmental and climate information in the Study area section.

3. "institutional ethics review board of the University of São Paulo School of Public Health (COEP FSP/USP, CAAE approval record 10457119.6.0000.5421, opinion 3408558)". Opinion?

Discussion:

"These authors showed that this increase is related to changes in temperature amplitude and is expected to be more pronounced in the north and northwest of the state, precisely the regions we found to be most affected."

I believe that the discussion about the greater incidence in the northern and northwestern regions of the state counties deserves further attention. What characteristics do these regions have that differentiate them from the rest of the state, in climatic and environmental terms, but also in terms of economic activities that they could include in contact with the scorpions? Different biomas? Are there studies on the density of these arthropods in the state? What do these works show for the regions with higher incidence? Different human development indexes?

Reviewer #2: The manuscript “Scorpion envenomation in the state of São Paulo, Brazil: Spatiotemporal analysis of a growing public health problem” by Lacerda et al. shows a dramatic increase in the incidence and mortality from scorpion envenomations between 2008 and 2018. The study aims to identify areas and populations at risk of scorpion envenomation and death in order to promote decision-making by the health services.

My main concern is that the authors do not sufficiently discuss the limitations of their study, especially with regard to the collection and analysis of data provided by the São Paulo State Epidemiological Surveillance Center.

The methodology is relevant and well described.

The results are aggregated, which does not allow a precise view of the data by group of people (sex, age), region and their evolution over time. Data confidentiality must be balanced for with more detailed analysis and comparisons.

The discussion raises 3 hypotheses – classic but convincing – about the causes of the increase in incidence and mortality, in particular the expansion of T. serrulatus which is gradually replacing T. bahiensis due to the new environmental conditions, and the evolution of human activities leading to both attraction of scorpions and increasing exposure. In this regard, the evolution of human activity is likely to be more strongly involved than climate change, the impact of which would be more gradual and could not explain, for example, the sudden increase in incidence and mortality from 2014.

However, as I indicated above, the authors do not sufficiently address other possible explanations such as the insufficient reporting of cases which would have improved between 2008 and 2018 or a gradual evolution of the healthcare seeking behavior of the patients (see Chippaux. J Venom Anim Toxins Incl Trop Dis. 2015; 21:13). They do not seek to verify these quite surprising results using data provided by independent sources.

Two ways should be considered to validate these hypotheses.

On the one hand, the authors indicate that the risk increased in all regions of the state of São Paulo throughout the study period. First, it is necessary to verify that the variables of interest show similar or even parallel evolutions in the different parts of the state and that there are no areas of significantly higher incidence and / or mortality which could be explained by variations in environmental conditions (scorpion population, human activities) and / or the management of scorpion stings (specially to prevent severe outcomes or death). There can be no convergence of epidemiological parameters (in particular parallelism of incidence in different places) in all the regions resulting from the authors' hypothesis insofar as the situations and their consequences cannot be identical in all the regions of the state of São Paulo. However, the authors indicate that the increase is higher (without data being available) in some regions. They should compare the explanatory situations (abundance of T. serrulatus, human activities, environmental and sanitary conditions, accessibility of health facilities, climate change) between different regions showing the highest differences in incidence (e.g. between the northwest, center and southern regions of the state of São Paulo).

On the other hand, the authors should check whether the increase in incidence and case fatality rate observed during the same period in randomly selected health centers in different regions is similar to that reported by the São Paulo State Epidemiological Surveillance Center.

I disagree with the authors when they state that underreporting of scorpion stings, especially mild cases, can be considered to occur uniformly in the state of São Paulo. The reasons for underreporting are not equivalent depending on the place and the person in charge of the case report. The case report may be affected by incidence, particularly frequency of mild or moderate envenomation, perception of the case severity, individual interest for the topic, overwork, etc...

Moreover, the authors do not seek to explain the increase in mortality, nor the random distribution of deaths between regions. They should study the case fatality rate of scorpion envenomation in a few hospitals located in areas with higher mortality. The increased case fatality rate could be related to difficulties in managing envenomation, e.g. failure of the antivenom supply or lack of knowledge of treatment of scorpion envenomation.

Assuming that the authors cannot answer some of these questions, they could at least mention and argue them.

Finally, the authors do not offer practical recommendations and let the health authorities make any decision based on their results. I think it's up to the authors to guide health authorities based on their results and knowledge of the problem.

Reviewer #3: The article addresses a very important issue related to scorpion injuries in Brazil, and also in other regions of the world, which has been increasing progressively year by year. The object of the study was the state of São Paulo, located in southeastern Brazil and which has 645 municipalities divided into 17 regional health districts, from 2008 to 2018. During this period there was an increase in the number of accidents of 425%. The aim of the study was to analyze the temporal and spatial distribution of the occurrence of accidents to identify areas of greater or lesser risk in order to develop strategies to reduce the population's contact with these scorpions to avoid deaths in the most vulnerable group (children 0-9 years of age).

The authors calculated the annual incidence and mortality rate standardized by sex and age. They used the empirical local Bayesian method and Gi* statistics to standardize the incidence rates in the municipalities and identify high and low risks of agglomeration.

There was a higher incidence and mortality among men, but mortality was concentrated in children under 9 years of age, with 42 of the total 48 deaths (88%) occurring in this group. From the analysis obtained by the maps, it was observed that accidents occurred more in the northern and northwestern regions of the state in contrast to the other regions, in addition to showing that the incidence of cases increased in all regions of S.Paulo.

The discussion about why this is happening was quite comprehensive, in terms of increased urbanization, climate effects, housing conditions, poverty, T. serrulatus parthenogenesis, etc.

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Reviewer #1: No

Reviewer #2: Yes: Jean-Philippe Chippaux

Reviewer #3: Yes: Palmira Cupo

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Scorpion envenomation in the state of São Paulo, Brazil: Spatiotemporal analysis of a growing public health concern

PONE-D-21-37124R1

Dear Dr. Lacerda,

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,

José María Gutiérrez

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers are satisfied with the changes and improvements introduced in the revised version of this manuscript.

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

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: Yes

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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

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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: I recommend to accept as it is in this new version.

I recommend to accept as it is in this new version.

Reviewer #2: The revision of the article "Scorpion envenomation in the state of São Paulo, Brazil: Spatiotemporal analysis of a growing public health concern" by Lacerda et al. shows clear improvements. The remarks and suggestions I had made on the previous manuscript were all taken into account in the revised version. In my opinion, the paper can be published as is.

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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.

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

Reviewer #2: Yes: Jean-Philippe Chippaux