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. 2021 May 25;16(5):e0252058. doi: 10.1371/journal.pone.0252058

Trend and epidemiological patterns of animal bites in Golestan province (Northern Iran) between 2017 and 2020

Vahid Bay 1,#, Mehdi Jafari 1,2, Mohammad Reza Shirzadi 3, Ali Bagheri 4, Irvan Masoudi Asl 1,*,#
Editor: Amir Radfar5
PMCID: PMC8148354  PMID: 34033653

Abstract

Background

Rabies is one of the oldest zoonosis viral diseases, which still remains as one of the most important threats to public health in the 21st century.

Methods

This cross-sectional study examined epidemiologic features of all 33,996 cases of persons bitten by animals and referred to the rabies prophylaxis centers in Golestan province between March 2017 and March 2020. Factors included demographic information of the victim (age, gender, and occupation), type of invasive animals (dog, cat, and other types), time of bite (year, month, and hour), place of residence (urban or rural), and injury and treatment statuses. We also obtained national and provincial animal bite incidence data for all of Iran and for Golestan province for the longer interval 2013–2020 to examine broader time trends. We used SPSS version 19, QGIS version 3.1, and Excel 2013 to generate frequency distributions and descriptive statistics.

Results

The incidence rates of animal bites in Golestan province and Iran as a whole both increased smoothly. The latest incidence rate of animal bites in Golestan was 652 per 100,000 people, almost three times the overall national figure for 2020. Most cases of animal bites (67.6%) occurred in rural areas, and 36% of the victims aged under 19 years old. Dog and cat bites accounted for the great majority of cases (89% and 8%, respectively). The highest rate of animal bites was reported in the spring (30.8%). The lower limb was the most commonly bitten area in these individuals (64.6%). Of note, 87% of the cases received incomplete prophylactic post-exposure treatment, and 18% received immunoglobulin.

Conclusion

The increasing rates of animal bites in the study area as well as the higher rate compared to the national average indicates the need for further review of animal bite control programs.

Introduction

Rabies is a zoonosis viral disease causing encephalomyelitis in humans and all warm-blooded mammals. This disease is one of the most important zoonosis and the oldest one, it’s the importance of which is due to its high lethality (100%) and economic costs [1–4].

The virus is distributed worldwide with the exception of Antarctica. As a result, about 10 million people annually bitten by animals worldwide are under the treatment for rabies prophylaxis [5,6]. The virus kills approximately 59,000 people worldwide each year, the majority of which occur in the populations of Africa and Asia [1].

In Iran, rabies has long been endemic to Iranian wildlife and frequently infects domestic animals [7]. In Iran, in the last 30 years, statistics of animal bites cases has increased with the incidence rate of 35 per 100.000 population in 1987 up to 177 per 100.000 people in 2016 [5].

According to the latest incidence status of animal bites in the country, Golestan province, along with Ardabil, North Khorasan, Charmahal-Bakhtiari provinces, are known as the provinces with high rates of animal bites. Notably, the incidence rate of animal bites in this province has increased from 503 cases in 2011 up to 557 cases per 100, 000 people in 2016 [5].

Therefore, this study aimed to investigate the trend and epidemiological patterns of animal bites in Golestan province.

Materials and methods

We conducted a cross-sectional study including all 33,996 cases of persons bitten by animals and referred to anti-rabies centers for prophylaxis in Golestan province from March 2017 to March 2020. We also compiled national and Golestan data on animal bites reported from 2013–2020 to study longer-term incidence trends.

The variables investigated in this study included demographic information of victims (age, gender, and occupation), type of invasive animals (dog, cat, and other types), time of onset of animal bite (year, month, and hour), place of animal bite (urban or rural), injury status (number of injured limb), and type of medical services provided. Golestan provincial data reflecting epidemiological factors were collected from the electronic animal bites registration system. National data on overall and province-specific incidence rates 2013–2020 were collected from the Center for Communicable Diseases Control of the Ministry of Health of Iran. After collecting the research’s data, they were entered into SPSS software version 19, QGIS version 3.1, Excel 2013, and descriptive statistics were the used to analyze the data.

This study was approved by the Research Ethics Committee of Iran University of Medical Sciences under NO IR.IUMS.REC.1398.716. The patients’ recorded information were kept confidential and all data was completely anonymized prior to access. This research was conducted in terms of the ethical principles and national norms and standards of conducting medical research in Iran.

Results

This study showed that the incidence of animal bites in Golestan province has increased from 492 cases per 100,000 people in 2013 up to 652 cases in 2019–2020. Additionally, the incidence of animal bites in Iran has increased from 196 to 282 in the above-mentioned period (see Fig 1). In Golestan province, Gomishan, Aliabad, and Maraveh-Tappeh counties had the highest incidence rates (934 to 957 cases per 100,000), while Minudasht County had the lowest incidence (391 cases per 100,000) in 2019–2020 (see Fig 2).

Fig 1. Incidence trend of animal bites per 100,000 people in Golestan province and in Iran.

Fig 1

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Fig 2. Animal bite incidence rates in Golestan counties (2019–2020).

Fig 2

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The results of this study show that 78.5% of the bitten animal individuals were men. The highest number of bites was related to the age groups of 1–9 and 10–19 years old with 18.8% and 19.2%, respectively, indicating that the rate of bites in age groups decreased with aging. In addition, 67.6% of the population were living in rural areas and 0.3% of them were non-Iranians (Table 1).

Table 1. Demographic information of the selected bitten animal patients.

variable Number percent
gender male 26688 78/5
female 7308 21/5
Residence area City 11050 32/4
Village 22946 67/6
Age group 1–9 6404 18/8
10–19 6512 19/2
20–29 5919 17/5
30–39 5631 16/5
40–49 3994 11/7
50–59 2953 8/7
60 years and older 2582 7/5
occupation Child 3638 10/7
Student 7740 22/7
housewife 4306 12/7
Employee 1288 3/8
Freelancer (farmer and rancher, worker, etc.) 4526 13/3
Other 2670 7/8
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This study showed that most of the animal bites were reported in spring and summer and the least in autumn and winter. As well, the highest rate of bites was reported between 12–18 o’clock with a rate of 37.1% and the lowest between 0–6 o’clock with a rate of 3.1% of the total bites. Temporal aspects of the animal bites are shown in Table 2.

Table 2. Temporal aspects of the animal bites.

variable Number percent
Bite season Spring 10471 30/8
Summer 8939 26/3
Fall 7547 22/2
winter 7039 20/7
Bite hours 0–6 1064 3
6–12 9350 27/5
12–18 12623 37
18–24 10960 32/2
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This study also showed that most of the animal bites were related to dog and cat with a rate of 96% of total bites; 49% of these animals had owners. Additionally, 58% of animals’ bites resulted in one injury and 28% of them caused two injuries. The most common bitten limbs were the hip and lower limbs with 64.6%. Also 87% of the patients received incomplete vaccine and 18% of the patients received immunoglobulin. During performing this study, one case of human rabies was reported. Information on the type of invading animal, place of the injury, and medical services provided are shown in Table 3.

Table 3. Information on the type of invading animal, place of the injury, and medical services provided.

variable Number percent
Invasive animal type Dog 30220 89
Cat 2718 8
Horses, ass, camels 220 0/7
cow, goats and sheep 357 1
Mice (types of mice, guinea pig, etc.) 328 1
Reynard, fox and wolf 52 0/2
Other animals 101 0/3
Place of injury Head, neck and face 678 2
Upper limbs (shoulder, arm, forearm, hand) 10465 30/8
Chest, abdomen, back 878 2/6
Hip and lower limbs 21976 64/6
Medical service provided vaccine complete vaccine 4351 12/8
incomplete vaccine 29576 87
Immunoglobulin 6119 18
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Discussion

According to the World Health Organization’s report, Asia and Africa have the highest rate of animal bites [1]. In Iran, the rate of animal bites in most areas has an increasing trend [5]. We confirmed the trend up to the present: the incidence of animal bites in Iran has increased from 196 to 282 from 2013–2020. The rate of increase for animal bites in Golestan province paralleled that of Iran as a whole, although at substantially higher rates than the national rate. The current study showed that the rate of animal bites in Golestan has increased from 492 cases in 2013 up to 652 cases per 100.000 people in 2019–2020. One of the reasons for the higher rate of animal bites in this province may be due to the location, which is in the center of animal husbandry and agriculture in Iran, naturally increasing the exposure of both humans and animals.

Our data showed that the most animal bites in Golestan occurred in men. Animal bites have also been reported more commonly in men in other Iranian studies [8–13]. In some countries, the rate is higher among women [14], probably reflecting economic and behavioral differences. Unlike western countries, keeping animals at home is usually avoided in Iran. Additionally, the high rate of bites in men can be related to their more presence in society due to occupational and non-occupational activities and more boldness in contact with animals.

According to the international data, most cases of human rabies have been reported in rural areas [1]. In the present study, 67% of the animal bites were reported from the rural community, which is consistent with most of the domestic data. However, in a study conducted in Abadeh, 57% of the bitten animal individuals were living in cities, which was not consistent with our study [8,9,11–13]. This issue can be due to the nature of rural occupations (husbandry and agriculture) as well as the presence of dogs in most rural households in the region.

In the present study, most of the bitten animal individuals were found to be related to the age groups of 1–9 and 10–19 years old, which included 38% of the bitten animal individuals. According to the international child data, the highest rate of animal bites by dogs belongs to children, the highest incidence rate of which is in mid to late childhood [14]. In other foreign studies conducted in India and Pakistan, cases in the age group under 15 and 17 years old were 34 and 48% of the bitten animal individuals, respectively, which was consistent with the data of our study [15,16]. However, in domestic studies, the most bites varied between the age groups of 10 to 40 years old [11], indicating the involvement of young age groups in this province, which can be due to the curiosity of this age group and provoking of animals.

According to the World Health Organization’s report, 76–94% of animal bites are caused by dogs in countries with low and medium incomes [14]. In our study, the most common causes of bites were dog and cat, which accounted for 89% and 8% of the bites, respectively. In a review study conducted in Arab countries, the dog was found as the most important cause of transmitting the virus to humans, with the exception of Oman, where the fox was introduced as the most important cause of transmitting the virus [17]. In other domestic studies, dog was also reported as the most common bite cause, which was consistent with our study [9,11–13,18]. This matter can be due to the large presence of dogs as domesticated animals in different human communities with different uses.

The present study showed that we mostly observe the highest rate of bites in the province in spring and summer, and the highest rate of bites has been reported in terms of daily hours between 12–18. In domestic studies, the highest rate of bites was mentioned to be in spring and summer and the lowest rate was reported in winter. Also, in a study conducted in Khorramshahr, the highest number of bites was reported between 12 to 18 o’clock, which its results were in line with our study [8,9,11,12,19]. The higher incidence of bites in spring and summer can be attributed to the expansion of husbandry and agricultural activities in spring and summer in this region.

In the present study, only one case of human rabies was reported in the studied geography. These data are consistent with data obtained from other parts of the country [5]. Considering the high incidence of animal bites in these areas, it can be said that the reason for the low rate of human deaths resulted from rabies is the appropriate coverage of post-exposure prophylaxis (PEP) services in the Iran’s health system.

According to the findings of this study, freelancers, students, housewives, and children had the highest rate of bites with 41, 24, 13, and 11%, respectively. In the studies conducted in Najafabad and Bardsir, freelancers and workers had the highest rate of bites followed by the students, which were in line with our study [13,18]. However, in a study conducted in Mashhad, after freelancers, people with governmental jobs recorded the highest rate of bites, part of which was inconsistent with our study [12]. In our study, the increased rate in bites in this group of people can be due to having freelance jobs such as animal husbandry and agriculture with animals like dog in the village, and also in students due to their specific age and curiosity to provoke animals.

Conclusion

Observing the increasing trend of animal bites in the study area (about three times higher than the national average) and consequent negative health, psychological, social, and economic effects caused by it, warn the need to review the current animal bites management programs based on the regional epidemiological patterns.

Supporting information

S1 File. Information file.

Information about: incidence rate (in cities, provinces and countries) and other epidemiological characteristics of animal bites.

(XLSX)

Click here for additional data file. (18.2KB, xlsx)

Acknowledgments

We appreciate the cooperation of the Department of Zoonosis Diseases of the Ministry of Health of Iran as well as the Deputy Minister of Health of Golestan University of Medical Sciences in conducting this study.

Data Availability

All relevant data are within the paper and its Supporting Information files.

Funding Statement

The author(s) received no specific funding for this work.

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Decision Letter 0

Amir Radfar

12 Feb 2021

PONE-D-20-38907

Trend and epidemiological patterns of animal bites in Golestan Province (North Iran) between 2017 and 2020

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Reviewer #2: Partly

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Reviewer #1: No

Reviewer #2: Yes

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Reviewer #1: Thank you for submitting this manuscript.

GENERAL

Please add page and line numbers to the document. It makes it much easier for reviewers to cite specific parts for comments and queries.

Please indent the first line of each paragraph. That will make the manuscript easier to follow.

I think that the manuscript would benefit from the services of an English-language editor. It could be more concise and clear.

METHODS

The source data from Golestan and from the entire nation should be described more clearly. I would refer to incident animal bite cases for all Iran (including Golestan) 2013-2020; and incident animal bite cases plus relevant epidemiologic features from Golestan 2017-2020.

It seems that the Golestan data set might benefit from further analysis. Multiple regression analysis would reveal the strength of associations between the various demographic and animal features and animal bites. Can you consult with a biostatistician on this matter?

TABLES

In Table 1, I think the factor Nationality can be deleted.

The title of Table 2 could be better: “Temporal aspects of the animal bites.”

Tables 2 and 3 have been switched. The text has Table 2 as the type of biting animal, but that information is shown in current Table 3.

In Table 3, the data on number and percent are switched from their proper headings.

RESULTS

Figures 1 and 2 are shown, but you say little about them. Why are they important? Can you elaborate a bit?

After Table 2, there is text on the completeness of treatment at the clinics. This seems extremely important to me. What is known about the outcomes of treatment? What can be done to improve the performance of the treatment services? Is the rabies service equally accessible in the different parts of Golestan? You do not show data on these points, and you do not discuss services.

DISCUSSION

I would delete the first sentence. You stated this in the Introduction.

A summary of your incidence data might be: “The rate of increase for animal bites in Golestan province parallels that in Iran as a whole, while the provincial incidence rate is substantially higher than the national rate.“

The final 2 words in the Discussion are out of place.

Reviewer #2: Dear author, in my point of view there are some points regarding your manuscript;

Would you please let me know that in cross sectional study design, can we calculate incidence?

In the method you mentioned that you used descriptive study such as mean and SD but I could not see it in the results.

In the table there are some values like 88/9, 1/1 which is not understandable.

It also need English editing

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Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2021 May 25;16(5):e0252058. doi: 10.1371/journal.pone.0252058.r002

Author response to Decision Letter 0

11 Mar 2021

Dear Reviewers

We read your comments and made the requested corrections

- Details of the corrections are listed in the Response to Reviewers file.

- Referees' corrections are marked in highlighted form. (In Revised Manuscript with Track Changes file)

- Professional text editor corrections are also marked as Review Markup (In Revised Manuscript with Track Changes file)

- The letter of the professional editor certificate is also attached.

Thank you for your consideration of this manuscript.

Sincerely:

Irvan Masoudi Asl

Attachment

Submitted filename: Response to Reviewers.docx

Click here for additional data file. (20.4KB, docx)

Decision Letter 1

Amir Radfar

1 Apr 2021

PONE-D-20-38907R1

Trend and Epidemiological Patterns of Animal Bites in Golestan Province (Northern Iran) between 2017 and 2020

PLOS ONE

Dear Dr. masoudiasl,

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.

ACADEMIC EDITOR: Please address all comments made by reviewers . I am interested to see a detailed response to the comment made by reviewer #2.

Please submit your revised manuscript by May 16 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Amir Radfar, MD,MPH,MSc,DHSc

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

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: (No Response)

**********

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: Partly

**********

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

Reviewer #1: Yes

Reviewer #2: N/A

**********

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: No

Reviewer #2: Yes

**********

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: No

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: Thank you for your revisions; the manuscript is much improved! I would like to suggest some further edits for clarity and concision. I also have one question about rabies vaccination and post-exposure prophylaxis.

ABSTRACT

Background : Rabies is one of the oldest zoonosis viral diseases, which still remains as one of the most important threats to public health in the 21st century.

Methods : This cross-sectional study examined epidemiologic features of all 33,996 cases of persons bitten by animals and referred to the rabies prophylaxis centers in Golestan province between March 2017 and March 2020. Factors included demographic information of the victim (age, gender, and occupation), type of invasive animals (dog, cat, and other types), time of bite (year, month, and hour), place of residence (urban or rural), and injury and treatment statuses. We also obtained national and provincial animal bite incidence data for all of Iran and for Golestan province for the longer interval 2013-2020 to examine broader time trends. We used SPSS version 19, QGIS version 3.1, and Excel 2013 to generate frequency distributions and descriptive statistics.

Results : The incidence rates of animal bites in Golestan province and Iran as a whole both increased smoothly. The latest incidence rate of animal bites in Golestan was 652 per 100,000 people, almost three times the overall national figure for 2020. Most cases of animal bites (67.6%) occurred in rural areas, and 36% of the victims aged under 19 years old. Dog and cat bites accounted for the great majority of cases (89% and 8%, respectively). The highest rate of animal bites was reported in the spring (30.8%). The lower limb was the most commonly bitten area in these individuals (64.6%). Of note, 87% of the cases received incomplete prophylactic post-exposure treatment, and 18% received immunoglobulin.

Conclusion : The increasing rates of animal bites in the study area as well as the higher rate compared to the national average indicates the need for further review of animal bite control programs.

INTRODUCTION

I would re-write the first sentence of the second paragraph thus: The virus is distributed worldwide with the exception of Antarctica. Then the next sentence can be deleted.

I think the first sentence of the final paragraph of the Introduction can be deleted.

METHODS

I would shorten the first paragraph:

We conducted a cross-sectional study including all 33,996 cases of persons bitten by animals and referred to anti-rabies centers for prophylaxis in Golestan province from March 2017 to March 2020. We also compiled national and Golestan data on animal bites reported from 2013-2020 to study longer-term incidence trends.

I would shift one sentence to make this the first sentence of the second paragraph:

Golestan provincial data reflecting epidemiological factors were collected from the electronic animal bites registration system.

I would re-write the sentence that currently begins with “As well, national data...” thus:

National data on overall and province-specific incidence rates 2013-2020 were collected from the Center for Communicable Diseases Control...

RESULTS

In the first paragraph, I would re-write the sentence that currently begins “Of note...”:

In Golestan province, Gomishan, Aliabad, and Maraveh-Tappeh counties had the highest incidence rates (934 to 957 cases per 100,000), while Minudasht county had the powest incidence (391 cases per 100,000) in 2019-2020 (see Figure 2).

I would make the names of the Figures more specific:

Fig.1. Incidence trend of animal bites per 100,000 people in Golestan province and in Iran

Fig. 2. Animal bite incidence rates in Golestan counties (2013-2020)

In the paragraph that describes the data in Table 1, if you add (Table 1) to an earlier sentence, you can delete the last sentence that currently reads “Some demographic information of the patients are shown in Table 1. That sentence does not really add much to the text.

In the text on Table 2, and in the Table itself, I think the hour intervals should be 0-6, 6-12, 12-18, and 18-24.

In the paragraph discussing Table 3, I think you should move the first two sentences should be moved to the end of the paragraph. That way, the structure of the text and of the Table are the same.

DISCUSSION

I would re-structure the first paragraph thus:

According to the World Health Organization’s report, Asia and Africa have the highest rate of animal bites [1]. In Iran, the rate of animal bites in most areas has an increasing trend [5]. We confirmed the trend up to the present: the incidence of animal bites in Iran has increased from 196 to 282 from 2013-2020. The rate of increase for animal bites in Golestan province paralleled that of Iran as a whole, although at substantially higher rates than the national rate. The current study showed that the rate of animal bites in Golestan has increased from 492 cases in 2013 up to 652 cases per 100.000 people in 2019-2020. One of the reasons for the higher rate of animal bites in this province may be due to the its location, which is in the center of animal husbandry and agriculture in Iran, naturally increasing the exposure of both humans and animals.

I would re-write some of the next paragraph:

Our data showed that the most animal bites in Golestan occurred in men. Animal bites have also been reported more commonly in men in other Iranian studies [8-13]. In some countries, the rate is higher among women [14], probably reflecting economic and behavioral differences. Unlike western countries, keeping animals at home is usually avoided in Iran. <additionally, activities="" and="" animals.="" be="" bites="" boldness="" can="" contact="" due="" high="" in="" men="" more="" non-occupational="" occupational="" of="" presence="" rate="" related="" society="" the="" their="" to="" with="">

<>I hope you can explain what you mean in the final sentence above; it is unclear to me.

Near the end of the Discussion, bottom of page 7, you write that only one case of human rabies resulted from this very large number of bites. You speculate that this likely resulted from the rather complete coverage of POST-exposure prophylaxis. But your own data in Table 3 shows that the great majority of cases had incomplete vaccine provided, and few received immunoglobulin. It seems very inconsistent to me. Perhaps all pet dogs and cats are vaccinated, thereby resulting in PRE-exposure prophylaxis? This is my big question, and I hope you can clarify it for me and other readers.

Finally, in the List of Tables and the List of Figures, please use the actual titles and not different wording.

Thank you for considering my suggestions!</additionally,>

Reviewer #2: Dear Author,

I could not find anything in your reference about calculation of incidence in cross sectional study. In my point of view we can not calculate incidence in cross sectional study but we can calculate prevalence. for calculation of incidence we have to conduct cohort study.

**********

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: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2021 May 25;16(5):e0252058. doi: 10.1371/journal.pone.0252058.r004

Author response to Decision Letter 1

11 Apr 2021

Dear Reviewers

We read your comments and made the requested corrections

- Details of the corrections are listed in the Response to Reviewers file.

- Referees' corrections are marked in highlighted form. (In Revised Manuscript )

Thank you for your consideration of this manuscript.

Sincerely:

Irvan Masoudi Asl

Attachment

Submitted filename: Response to Reviewers.docx

Click here for additional data file. (22KB, docx)

Decision Letter 2

Amir Radfar

29 Apr 2021

PONE-D-20-38907R2

Trend and Epidemiological Patterns of Animal Bites in Golestan Province (Northern Iran) between 2017 and 2020

PLOS ONE

Dear Dr. masoudiasl,

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.

ACADEMIC EDITOR: Please address all comments made by Reviewer #1

Please submit your revised manuscript by Jun 13 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Amir Radfar, MD,MPH,MSc,DHSc

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

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

**********

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

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

**********

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 manuscript looks great! Thank you. May I suggest a few minor changes at this final stage?

In Table 2, it looks like the lowest bite rate was from midnight to 6AM (3%). I think you need to revise that sentence at the bottom of page 4.

In Table 2, can you change the label from ‘free’ to ‘freelancer’? That way, it will match the text in the Discussion.

At the top of page 5, the sentence could be made clearer if you write: “...96% of total bites; 49% of these animals had owners.”

In the middle of page 7 where you discuss the extraordinarily low death rate from rabies, the text appears inconsistent with the data on completeness of treatment. But the explanation you kindly provided in your response to reviewers taught me why there is no real inconsistency. (I am not a rabies expert!) I suggest that matters would be clarified in the article if you add some of the text from your response to reviewers here in the Discussion.

Reviewer #2: all of the comments are addressed .

**********

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: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2021 May 25;16(5):e0252058. doi: 10.1371/journal.pone.0252058.r006

Author response to Decision Letter 2

6 May 2021

Dear Reviewers

We read your comments and made the requested corrections

- Details of the corrections are listed in the Response to Reviewers file.

- Referees' corrections are marked in highlighted form. (In Revised Manuscript )

Thank you for your consideration of this manuscript.

Sincerely:

Irvan Masoudi Asl

Attachment

Submitted filename: Response to Reviewers.docx

Click here for additional data file. (17.6KB, docx)

Decision Letter 3

Amir Radfar

10 May 2021

Trend and Epidemiological Patterns of Animal Bites in Golestan Province (Northern Iran) between 2017 and 2020

PONE-D-20-38907R3

Dear Dr. masoudiasl,

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.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Amir Radfar, MD,MPH,MSc,DHSc

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Acceptance letter

Amir Radfar

17 May 2021

PONE-D-20-38907R3

Trend and Epidemiological Patterns of Animal Bites in Golestan Province (Northern Iran) between 2017 and 2020

Dear Dr. Masoudi Asl:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Amir Radfar

Academic Editor

PLOS ONE

Associated Data

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

    Supplementary Materials

    S1 File. Information file.

    Information about: incidence rate (in cities, provinces and countries) and other epidemiological characteristics of animal bites.

    (XLSX)

    Click here for additional data file. (18.2KB, xlsx)
    Attachment

    Submitted filename: Response to Reviewers.docx

    Click here for additional data file. (20.4KB, docx)
    Attachment

    Submitted filename: Response to Reviewers.docx

    Click here for additional data file. (22KB, docx)
    Attachment

    Submitted filename: Response to Reviewers.docx

    Click here for additional data file. (17.6KB, docx)

    Data Availability Statement

    All relevant data are within the paper and its Supporting Information files.

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