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. 2022 Jan 13;17(1):e0260326. doi: 10.1371/journal.pone.0260326

Geographical accessibility to the supply of antiophidic sera in Brazil: Timely access possibilities

Ricardo Antunes Dantas de Oliveira 1,*,#, Diego Ricardo Xavier Silva 1,#, Maurício Gonçalves e Silva 2,#
Editor: Ahmed Mancy Mosa3
PMCID: PMC8757981  PMID: 35025873

Abstract

Snakebite accidents are considered category A neglected tropical diseases. Brazil stands out for snakebite accidents, mainly in the Amazon region. The best possible care after snakebite accidents is to obtain antiophidic sera on time. And the maximum ideal time to reach it is about 2 hours after an accident. Based on public health information and using a tool to analyze geographical accessibility, we evaluate the possibility of reaching Brazilian serum-providing health facilities from the relationship between population distribution and commuting time. In this exploratory descriptive study, the geographic accessibility of Brazilian population to health facilities that supply antiophidic serum is evaluated through a methodology that articulates several issues that influence the commuting time to health units (ACCESSMOD): population and facilities’ distribution, transportation network and means, relief and land use, which were obtained in Brazilian and international sources. The relative importance of the population without the possibility of reaching a facility in two hours is highlighted for Macro-Regions, States and municipalities. About nine million people live in locations more than two hours away from serum-providing facilities, with relevant variations between regions, states, and municipalities. States like Mato Grosso, Pará and Maranhão had the most important participation of population with reaching time problems to those units. The most significant gaps are found in areas with a dispersed population and sometimes characterized by a high incidence of snakebites, such as in the North of the country, especially in the Northeastern Pará state. Even using a 2010 population distribution information, because of the 2020 Census postponement, the tendencies and characteristics analyzed reveal challenging situations over the country. The growing availability of serum-providing health facilities, the enhanced possibilities of transporting accident victims, and even the availability of sera in other types of establishments are actions that would allow expanding the possibilities of access to serum supply.

Introduction

In 2017, the World Health Organization classified snakebite poisoning as category A neglected tropical diseases [1], which spurred studies on appropriate prevention, implementable interventions, and resources to be allocated nationally and regionally [2].

Areas such as the Western Amazon, Sub-Saharan Africa, Southeast Asia, and Eastern Australia have many snake species. However, only some countries have effective sera for specific treatment by poisoning type [3]. In many cases, people use traditional therapies and treatments instead of the medical network and health centers, which leads to higher mortality and amputation rates. The predominance of such behavior is highlighted in African countries [2].

The morphoclimatic features of the Brazilian territory is related to the presence of snakes in all its Biomes. The profile of the population most affected by snakebite accidents has remained stable throughout the twentieth century, consisting of male rural workers aged 15–49 years [4].

Brazil registered a mean of 27,000 records of snakebites from 2001 to 2012 [5], with similar values until 2019, based on Notifiable Diseases Information System (SINAN) information [6]. Also, according to this system, the highest number of cases in recent years occurred in 2019, with 30,482, and the lowest in 2014, with 26,145.

The absolute majority, above 70% of the snakebite cases, were caused by the genus Bothrops, better known as Jararaca, followed by the genus Crotalus (7.5%), popularly identified as Cascavel. It should be noted that 11.5% of the cases failed to register information about the snake genus in SINAN [6] during the 2007–2019 period.

Also, according to SINAN [6], the regional distribution of the number of snake accidents is quite different when considering the totals from 2007 to 2019. The North region recorded 32% of the 367,199 accidents in the period, followed by the Northeast and Southeast, with 25.7% and 23.8%, respectively. Minor shares were registered in the Midwest (10.2%) and South (9%) regions.

Geographical accessibility is part of the broader, diverse and complex concept of access to health care [7, 8]. The evaluation of the quality of access to care involves not only geographical accessibility to health services, but also the availability of the them, its viability to obtain and the acceptability of care [911]. These various dimensions and its sub dimensions have multiple interactions and impacts on each other [9]. Specifically, geographical accessibility is related to the spatial distribution of health facilities and the time to access them, considering the travel costs related [10].

As many other health care types, the time to access health facilities and travel costs hinder access [1012] to the supply of antiophidic sera. The geographical accessibility to modern and appropriate treatments in snake accidents is essential to ensure care [3]. A resolutive health unit two hours away increases the likelihood of successful treatment [13].

While snakebite poisoning is recognized as a neglected disease [1], significant lacunas are identified in the recent literature regarding geographic accessibility to health facilities that offer antiophidic sera. Few materials have been found in Brazil and international literature. Snakebite accidents and therapeutic care were recently analyzed in municipalities like Vassouras (RJ) [14] and Cruzeiro do Sul (AC), in the Brazilian Amazon [15]. Although they did not directly highlight geographic accessibility, they addressed the conditions for obtaining treatment in the respective municipalities. These analyses were performed on a local scale, distinct from our approach.

An example from international literature is the analysis of populations with difficult access to the supply of sera in Costa Rica, considering the distribution of poisonous snake species, the incidence of accidents, and commuting time to access health facilities [13]. A geoprocessing software articulated topography information and transport routes and modes to calculate the time for accessing services.

Elements such as the spatial distribution of the population, the road network, the location of health centers and hospitals, and commuting time must be considered for a proper identification of the possible access to facilities providing antiophidic sera. Thus, the study aims to analyze the geographical accessibility to Brazilian serum-providing health facilities from the relationship between population distribution and commuting time.

Methods

This exploratory descriptive study was developed with the use of public health statistics and other information, through ACCESSMOD 5 [16], a tool made available by World Health Organization to analyze the time/distance relationship in accessing health services. Based on travel time cost surface models, this software integrates information from different dimensions that influence commuting time, such as relief, routes and means of transportation, land use and population distribution [17, 18]. It differs from other methods because it considers the population based on a statistical grid instead of municipal centroids and distances from the different commuting types and their respective average speeds, which is not employed in most of the literature on the issue [17].

Information from different sources was used to analyze geographical accessibility to serum supply. The sources and preparation of each data to meet the study’s needs are described below. Noteworthy is that all data have been redesigned for the Albers Equivalent Projection, with the same parameters used in the preparation of the IBGE statistical grid [19] (Central Meridian: -54°; Latitude of Origin: -12°; 1st Standard Parallel: -2°; 2nd Standard Parallel: -22°; Origin E: 5.000.000, Origin N: 10,000,000). Another common fact is that all data processing procedures were performed in Quantum GIS 3.4.1 and its extensions.

Population

The population data derive from the IBGE statistical grid (IBGE, 2016) [19] and refer to 2010 since it was based on the last Demographic Census in Brazil. The base initially has a resolution of 200 meters for urban areas and 1 kilometer for other areas. A 200-meter resolution grid was created for Brazil as whole, perfectly superimposed on the statistical grid for use in the study. Centroids were generated for all of these features (squares). Then, these centroids were gathered spatially with the statistical grid to incorporate population and identification information into them. Subsequently, the population data of the centroids that fell into squares in the one-kilometer statistical grid was divided by 25 (5 rows x 5 columns) since that the number of centroids fits in a grid of this size. With a resolution of 200 meters and the 2010 population supplied, the resulting centroid grid was converted to the raster format.

Routes

The routes used in the study are part of the 2018 Open Street Map (OSM) database [20], basically from two files: gis.osm_roads_free_1 and gis.osm_waterways_free_1, both in shapefile format. The classes of land routes were used in the first, and waterways were considered in the second. The features of this last file have been filtered to employ only those internal to the states of the North region, except for Tocantins, since, in many cases, they are the main and only access routes in that part of the country. The resulting two files were merged and kept in the shapefile format. Mean travel speeds were also assigned according to the classes of the OSM files, ranging from a maximum of 80 km/h on main roads to a minimum of 5 km/h on pedestrian routes, considering 20 km/h for commuting in rivers and channels.

Land use

As in the route data, land use also derives from the OSM database [20], file gis.osm_landuse_a_free_1. The original data did not change significantly since it was only redesigned and converted to the raster format. The “.img” format and “code” target field (that is, the land-use class code) were used as parameters to create the file. The speed considered for all classes was 1 km/h.

Digital Elevation Model (DEM)

The influence of the relief on the time to reach a facility with an offer of antiophidic sera was considered in this study. Data from NASA’s SRTM (Shuttle Radar Topography Mission) [21], version 3, with three seconds of arc size, were used to generate the DEM tracking, which is equivalent to 90 ground meters on the Equator. The original data were merged and resampled to 200 meters to match the other themes used in the study.

Facilities

The health facilities offering antiophidic sera were provided by the Toxic-Pharmacological Information System (SINITOX) team [22], based on the National Register of Health Establishments (CNES) database [23, 24] and later georeferenced with automatic and manual methods, which in some cases demanded visual confirmation through Google Maps [25] and Google Street View [26], spatially concentrated in the state of Pará. We managed to position 2,198 units with capacity to provide this care type in Brazil at the end of the georeferencing process of health units. We had to consider the location coordinates of the local area where 25 facilities had their registered address since it was impossible to obtain their exact location.

Distance and time to reach health facilities calculation

Population commuting time to reach health facilities was calculated using integrated information on population distribution, routes, land use, digital elevation model, and health facilities. The procedure was performed using the ACCESMOD 5 software [16], freely disseminated by the World Health Organization, that provides the simulation of the traveling time to the nearest health facility considered, using a travel time cost surface model. After the upload of the raster files of all the elements described above, the software generates catchment areas of health facilities using the Dijkstra least-cost path algorithm [17, 27].

The use of ACCESSMOD [16] allows further refinement when considering several dimensions for calculating the relationship between population and commuting time since it considers the relief, the speed by route type, and land use. As a result, the software calculates more than Euclidean distances as it is based on the routes and the elements influencing the movement and commuting time to reach serum-providing facilities, that is, much closer to the daily reality of the population. Also, unlike the use of points to locate the population, the statistical grid considers the spatial distribution of the population in the territory, which also affects the time-distance relationship. Thus, it contributes to the analysis of access to serum-providing facilities in the country, using a tool that allows integrating several factors that influence travel time and costs.

Snakebite accidents’ information

Besides data used to develop the analysis in ACCESSMOD [16], information about accidents by snake type and municipality, based on place of residence, from 2007 to 2019 was also considered. Data were aggregated by broader spatial scales. This information derives from the Information System on Notifiable Diseases (SINAN) [6]. The period was selected due to the greater compatibility from the first year of the series than the previous information. Certainly, there are problems and differences about the quality of information about snakebite accidents in SINAN [28, 29], but this health information system has been centralizing the information about notifiable diseases since the beginning of the century [28] and improving its coverage in the last years [30], in all Brazilian States. There is a lack of more recent evaluation about the quality and coverage of the information about snakebite accidents in Brazil.

The results are presented basing on the share population without possibility of reaching a serum providing health facility in two hours for different geographical areas, namely, Brazil, Macro Regions, States, and municipalities, to better characterize the issue.

This analysis focused on access to antiophidic sera, however, it could also be developed to address access to other types of services. The technique allows discussing geographic accessibility under different approaches, considering the location of the facilities and commuting time, and identifying and locating gaps for the care type highlighted here. Therefore, it aims to contribute to the debate on access to health services in the country and points out investment needs to expand the serum supply.

Results

The analysis of the geographical accessibility to health facilities that can provide antiophidic serum is based on the use of information about Population Distribution, Routes, Land Use, Digital Elevation Model, and Health Facilities. Fig 1 registers the maps of each one of these components.

Fig 1.

Fig 1

Health Facilities (a), Statistical Grid (b), Digital Elevation Model (c), Routes (d) and example of Land Use (e). Source: Health Facilities: Toxic-Pharmacological Information System (SINITOX), Statistical Grid: IBGE, Digital Elevation Model: NASA, Background: U.S. Geological Survey/National Geospatial Program, and Transportation and Land Use Routes: Open Street Map.

There is an association between the distribution of population (b), routes (d) and health facilities that can provide serum. More populated parts of the country have more distributed facilities with more expressive availability of routes. The Amazon region, in the northern part of the country, has a spatially concentrated distribution of facilities and more complex circulation or transportation, because in many cases the only available mean are waterways. The Digital Elevation Model (c) was included because ACCESSMOD [16] allows the consideration of effects of going up or down at the roads and the parts of the country which have a mountainous relief. The last map is an example of the Land Use information, just to register its detailing diversity.

The results address how much of the Brazilian population has the possibility to reach serum-providing facilities up to two hours. To this end, several spatial scales were considered to identify gaps. On a national scale, 5% of the Brazilian population could not reach an unit within two hours, which in absolute terms represented about 9.8 million people. Fig 2 shows the distribution of these areas in the country.

Fig 2. Population reach to antiophidic treatment by commuting time, Brazil.

Fig 2

Source: IBGE; ICICT/Fiocruz. Organization: Maurício Silva and Diego Ricardo Xavier.

In all capital cities and their immediate surroundings, the population could reach a facility within two commuting hours. Concerning inland regions of the states, those with the most significant territorial extensions had the most extensive voids, which was the case of almost all states in the North region, Mato Grosso, Piauí, and Ceará.

The reaching patterns are different between the main regions and, consequently, between the states and the Federal District. The North has the highest proportion of the population (11.8%) more than two hours away, which in absolute terms represents 1.8 million people. In the Northeast, about 5.9 million people (11.4% of the population) are more than two hours away from a facility for antiophidic treatment. In the Midwest, 6.4% of the population are in this situation (885 thousand people), while in the South, this percentage drops to 3.5% (926 thousand people). Finally, in the Southeast this situation is registered only by 0.3% (267 thousand people).

Considering the States (Fig 3), Maranhão, with 29%, which represents 1.83 million people, has the most significant proportion of the population with more than 2 hours to reach an antiophidic care health unit. Also, the state of Rondônia with 28% of its population (424 thousand people) and Mato Grosso with 26% (775 thousand people) stand out. In the state of Ceará, 22% of the population stands more than two hours away from antiophidic treatment. However, this represents 1.82 million people, a number similar to Maranhão. When considering only absolute numbers, also relevant are the values observed in the states of Rio Grande do Sul, with 895 thousand people (8.6%), Pará, with 730 thousand people (10.2%), and Paraíba, with 694 thousand people (18.9%), more than 2 hours away from a health unit with antiophidic care.

Fig 3. Population (%) more than 2 hours away from antiophidic treatment, by Brazilian states.

Fig 3

Note: Own elaboration. Sources: IBGE; ICICT/FIOCRUZ.

The last spatial unit used to present the results are municipalities (Fig 4). In this scale, 354 municipalities registered more than 75% of the population without coverage for antiophidic care within a maximum of two commuting hours. Forty-four municipalities stood between 50% and 75% and 150 in the class between 30% and 50%. Four hundred and four municipalities had good coverage, from 15% to 30%, and 4,617 municipalities had less than 15% of uncovered population. Noteworthy are inland areas of the states of Ceará, Paraíba, Piauí, and Rio Grande do Norte, the central region of the state of Mato Grosso and Rondônia, west of Maranhão and Roraima, west of Amazonas, and the extreme South of Rio Grande do Sul.

Fig 4. Population (%) more than 2 hours away from antiophidic treatment, by Brazilian municipalities.

Fig 4

Note: Own elaboration. Sources: IBGE; ICICT/FIOCRUZ.

For comparative purposes, Fig 5 shows the number of snakebite accidents by Brazilian municipality from 2007 to 2019. Except for significant population concentrations such as São Paulo (SP), Salvador (BA), and the Federal District (DF), which also can register better conditions of notification, most of the municipalities with many accidents are found in the North of the country. Both capitals, such as Manaus (AM), Belém (PA), Rio Branco (AC), Porto Velho (RO), and Macapá (AP), and inland cities are noteworthy, mainly in Pará. It is interesting to highlight a relevant concentration of municipalities with high amounts of accidents in the Lower Amazon basin and along its course in western Pará and eastern Amazon, besides the Solimões River and Upper Negro River, in the Western Amazon.

Fig 5. Number of snakebite accidents from 2007 to 2019 in Brazilian municipalities.

Fig 5

Note: Own elaboration. Source: SINAN/DATASUS.

Based on information from SINAN [6] about snakebite accidents in 2019 and the municipal population estimated by IBGE for 2019 [31], rates were calculated per thousand inhabitants per municipality and are available in a S1 Appendix, that also brings the share of population with accessibility in more than two hours. The Federal District (DF), São Paulo (SP) and Salvador (BA) registered rates below 0.05 accidents per thousand inhabitants, while small municipalities in the Amazon and the Northeast registered values above 3 per thousand. Worth highlighting places like Alto Alegre (6.38) and Uiramutã (5.87) in Roraima, Severiano Melo in Rio Grande do Norte (4.92), Mazagão (4.21) and Itaubal (3.09) in Amapá, Recursolândia in Tocantins (3.96), Afuá in Pará (3.37), and Arame in Maranhão (3.03).

Forty-six municipalities registered incidence rates of 2 or more snakebite accidents in 2019, generally with rural activity patterns [32]. Mostly of them (29) are located in the North Region, characterized by the Amazon Forest, 13 in the state of Pará. The worst condition in terms of population share with more than hours to reach a health facility that provides serum, is registered by northern municipalities, where 13 has more than one third of the population with access difficulties, highlighting four of them with more than 90% in this situation: Anajás (PA), Cutias and Itaubal (AP) and Japurá (AM).

Municipalities with expressive incidence rates but located in other regions of Brazil registered better conditions of geographical accessibility, with shares inferior to 13% of population more than hours away. Only Severiano Melo (RN), a northeastern municipality, had a more relevant participation of this situation (28.9%).

When comparing Figs 4 and 5, combining the most significant difficulties in accessing facilities to the most considerable amounts of snakebites from 2007 to 2019, we observe that the greatest challenges in obtaining serum are found in the Lower Amazon, between the states of Pará and Amapá and west of Manaus (AM), along the Solimões River. The articulation between environmental conditions that lead to a more significant presence of snakes and commuting hardships encumber the supply demand. Thus, it is necessary to expand serum supply sites in these regions with a logic that considers accessibility by the means of transportation available in the respective locations.

Discussion

In Brazil, geographic accessibility is a very important issue due the continental dimension of the country and the existence of vast, remote areas with isolated populations and essential challenges for people’s commuting. In this context, the North stands out and has the highest number of snake accidents and the most significant travel challenge, although it is the least populous region in the country.

The national outlook of accessibility to antiophidic sera reveals a high population coverage, allowing geographic access on time to health facilities that offer this service, what is related to the possibility of reducing deaths and sequelae from these accidents.

This network of serum-providing health facilities is been implemented through years of investment [4], what significantly changed the situation in the supply of sera in the country compared to the one addressed for the state of São Paulo just over three decades ago [33], in combination with a stable national production of antiophidic serum at public institutions [28, 34]. The expanded serum supply network correlates with government investment and the results achieved in the expected outcome, which is case recovery [34]. These studies consider that time between accident and treatment is preponderant for a better prognosis of the patient [13, 29]. While the treatment may have good results two hours after the snakebite accident, a higher success rate can be achieved within this interval.

The segment of the population residing more than two hours away deserves attention since it exceeds 9 million inhabitants. The coverage patterns found in this study reveal that people with the most challenging access live in rural areas or with a predominance of native vegetation. Despite the continental size of Brazil vis-à-vis Costa Rica, the challenges for geographic accessibility to antiophidic sera are similar [13], according to an analysis that also used geoprocessing tools. People residing in remote areas with complex conditions of commuting and transportation (mountainous regions, tropical forests, other sparsely populated areas) characterize complex situations concerning timely access to health care.

Some regions of the country require efforts to expand the offer of antiophidic sera to the population. The first is located in the Northeast, especially in the inland municipalities of the states. The pattern of rural occupation based on small properties [32] puts a high population contingent without the availability of antiophidic serum, and Ceará and Paraíba are the highest priority for the installation of health units offering this service. Inland Piauí and Maranhão can also be mentioned in the same situation.

The Rio Grande do Sul situation is also worrying, even considering the low population density. However, due to the density of the urban network and the circulation routes, the transportation of the injured to the serum-providing sites becomes relatively more manageable since it would be sufficient to direct serum doses to the existing health units.

Another particular reality is that of northern Mato Grosso, where the sizeable rural property predominates [32]. It is a low population density area where municipalities have large extensions. Thus, focusing efforts only on making serum available in small urban centers may not be enough, and the articulation between government and farm owners is an additional option for timely delivery of antiophidic serum to rural workers in the region.

Finally, the expressive territorial extension of the Amazon, especially the inland region of the states of Acre, Amazonas, Rondônia, Roraima, Amapá, and eastern Pará, is characterized by an extensively dispersed population, with forests, and waterway commuting. Alternative actions should be considered in these areas, focusing on those based on the availability of antiophidic serum closer to the population and expanding the network of health facilities. Also, actions that implement an efficient distance integration (from the accident site to the nearest health unit) and agile rescue means that use speedboats or helicopters can become a more appropriate option in the Amazon reality.

In more than 100 years, studies on this theme show that the epidemiological profile of snakebite cases has not changed [4]. The cases occur more frequently at the beginning and the end of the year, in male rural workers aged 15–49 years, mainly affecting the lower limbs. Without an individual consideration of risk, the characterization of areas in the present study reveals situations of important incidence and low geographical accessibility, with concentration of rural activities, especially in the North, but also at the Northeast region and the state of Mato Grosso.

It is important to consider that the location of services hinders access to health services concerning supply, while the means of transportation available and commuting costs are related to demand [10, 11]. The travel time for obtaining antiophidic sera is related to all identified barriers and expresses critical challenges for obtaining resolutive care. All those questions are related to geographical accessibility, but access to health services is a much broader question [79] and in the case of antiophidic sera involves at least the actual availability of serum, which depends on production and distribution logistics.

The study has some limitations apart from not considering the availability of serum, which would depend on qualified information on antiophidic sera distribution. The postponement of Brazilian 2020 Demographic Census imposed the need of using population data of the last Census, in 2010. The difficulties to estimate the travel speed considering rivers and other waterways (a widespread situation in the Amazon Region) also brings difficulties to the present approach. Also, the fact that there is an interval between the snakebite accident and the access to transportation, that can imply in a significant preliminary delay is very relevant, with impacts in the two-hour time to reach treatment, but is impossible to infer in a national perspective.

Some Brazilian studies in Brazil have also proposed to assess the time from snakebite to patient care [14, 15]. However, these are local studies starting from a casualty base, and their various outcomes are observed, considering specific small-scale analysis units. The innovation of this study is observing on a national scale the population at a distance that, according to the literature, brings more significant harm to treatment. In this sense, care gaps that can direct interventions and, consequently, reduce the cases developing to death or significant sequelae to the patient are pointed out.

Conclusions

This study contributes with the analysis of geographical accessibility integrating several issues that influences commuting time and this can be developed for other healthcare networks. Other contributions are related to the analysis of access barriers linked to travel hardships, which imply several costs, and identification of places with investment needs to expand antiophidic sera offer, either by installing more health units or improving the injured transport conditions. In this perspective, the study can subsidize other studies about geographical accessibility and the actual academic and public policies debate about the questions that are dealt. Also, it is important to highlight that the analysis also shows the relevance of well-structured and updated Health Information Systems for planning health actions and their potential use.

Supporting information

S1 Appendix. Snakebite accidents, population, incidence rate and uncovered population (%) by Brazilian municipalities, 2019.

(DOCX)

Data Availability

The datasets and basic map generated during the study development is available with no restriction at https://doi.org/10.7303/syn26042133. The Snakebite accidents data that support the findings of this study are available from SINAN - Notifiable Diseases Information System, at http://www2.datasus.gov.br/DATASUS/index.php?area=0203&id=29878153. The Statistical Grid data that support the findings of this study are available in IBGE - Brazilian Institute of Geography and Statistics, at https://portaldemapas.ibge.gov.br/portal.php#homepage. The road network and land use data that support the findings of this study are available from OPEN STREET MAP (OSM), at: https://www.openstreetmap.org/. The Digital Elevation Model data that support the findings of this study are available from Earth Data - Open Access for Open Science, at: https://earthdata.nasa.gov/eosdis/daacs/lpdaac. The health facilities data that support the findings of this study are available from CNES - National Register of Health Facilities, at http://www2.datasus.gov.br/DATASUS/index.php?area=0204&id=6906 The 2019 population estimates data that support the findings of this study are available in IBGE - Brazilian Institute of Geography and Statistics, at https://www.ibge.gov.br/estatisticas/sociais/populacao/9103-estimativas-de-populacao.html?=&t=o-que-e.

Funding Statement

RAD Oliveira have funding from Inova Fiocruz Program (https://portal.fiocruz.br/programa-inova-fiocruz), (Grant number: Inova Program VPPCB-008-FIO-18-2-48), a research support obtained in a selection occurred in 2018. The funds allowed the payment of scholarships to organize the datasets and the spatial information treatment, beyond the participation in congresses and seminars. The funding body had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Decision Letter 0

Ahmed Mancy Mosa

26 Jul 2021

PONE-D-21-22192

Geographical accessibility to the supply of antiophidic sera in Brazil: Timely access possibilities

PLOS ONE

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Reviewer #1: Yes

Reviewer #2: Partly

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: N/A

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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: Abstract

- Background must clearly describe the purpose of the study.

- Methods must describe: the type of study design and the method used (ACCESSMOD), the data collection and analysis, and the measures used in the description of Results, summarizing what was presented in the Methods section of the manuscript.

- In Results, the states that present the longest time to health units should be highlighted.

Background

- The paragraphs in lines 106-113 and 127-138 would be more suitable in the Methods section and not in the Background.

- The last paragraph of the Background should describe the purpose of the study.

Methods

- The type of study design must be described in the first paragraph.

- After the subtitle and paragraph referring to “Distance calculation”, it is necessary to describe in detail the tabulation and data analysis process, as well as the measures which were used, statistical tests and the level of significance considered.

- The authors used 3 distinct geographic analysis units: macro-regions, federative units (states and Federal District) and municipalities. This should also be described in Methods.

Results

- In lines 277-285, I suggest that the calculation of the incidence rate be revised, since the indicator in the DF, São Paulo and Salvador has been presented as 0.05. It would be more appropriate to work with the indicator per 100,000 inhabitants.

Discussion

It is important to discuss not only the innovation proposed by this study, but also its limitations, at the end of the section.

Reviewer #2: Snakebite accidents are, in some regions, relevant public health issues. The WHO's recognition, including this problem in the list of neglected tropical diseases, was an important step towards the production of more knowledge on the subject and, mainly, the mobilization of governments and other institutions to reduce the damage caused by this type of event. The manuscript has the merit of addressing this topic, which is of regional relevance in Brazil.

I understand that the central focus of the work and its strength are in the application of the method that analyzes the distance between health units and population distribution. As the author himself mentions, it could be used for other health situations. The problem is using this single analysis to base the entire discussion of the manuscript.The subject of snake accidents ends up being secondary and treated in a superficial way or weakly based on the results obtained from the performed analyses. Fundamental factors were left out or were superficially addressed, if we consider the endo f the title “Timely access possibilities.” For example, the availability of serum.

The manuscript ignores the limited availability of the serum and, therefore, assumes the existence of an unlimited amount of the product. It assumes that adequate allocation in health units would only lack evidence-based rationalization (the model presented, for example). Unfortunately, that's not the reality. The distribution of sera is fundamentally conditioned by its availability.

The WHO classification itself highlights this discussion. It is not just the affected population that defines an illness as neglected. The industry's insufficient investment as well. In the case of the production of serums, this is even more sensitive, since the production, usually, has to be regionalized according to the specificity of the snake species, with specific distribution.

Not every population more than two hours away from the health units that provide serum is under the same risk of snakebiting. The categorization of the most isolated populations in terms of risk would be essential to better qualify the analysis and enable a prioritization criterion to support decision-making and suggest “timely access possibilities” as the title says. Municipalities with higher incidences are briefly mentioned, but the discussion is not go further.

Furthermore, the quality of the information is not discussed. For example, when commenting on the large number of cases in the city of São Paulo, the author mentions only the large population of the city as an explanation and does not assess the possible effect on the notifications of the existence of very important references (regional and national) in the treatment of snakebite accidents, located in its territory.

For these reasons, it seems a little ambitious to discuss "timely access possibilities", based almost exclusively on the distance between the population and the health unit, without analyzing risk, serum availability, health system configuration, information quality.

There are some problems with the references. For example, information on the WHO classification of snakebites as a neglected tropical disease is referenced to the article "Longbottom J, Shearer FM, Devine M, Alcoba G, Chappuis F, Weiss DJ, Williams, DJ. Vulnerability to snakebite envenoming: A global mapping of hotspots. The Lancet. 2018; 392(10148): 673-84". However, the information is not from this article, which cites original information from WHO document "Report of the tenth meeting of the WHO Strategic and Technical Advisory Group for neglected tropical diseases. World Health Organization, Geneva2017".

In my opinion, the work presented allows discussing only the geographic distribution of the population in relation to the units that provide serum, without assuming that this analysis is sufficient to think about strategies for expanding access to services.

Reviewer #3: This manuscript assessed the accessibility to antiophidic sera in the Brazilian context. Snakebite accidents are a neglected public health problem in the country; the knowledge aimed at by the present study is certainly relevant to health policy and planning in many remote and rural areas. The text is well written and can be read smoothly. However, it is poorly organized.

The Introduction is unnecessarily too large. It should have ended in line 97, after stating the study objective. Using different geographical areas (lines 97-8) in the approach is related to Methods, not the Introduction. That this analysis allows discussing accessibility to other health services (lines 99-105) is a matter for Discussion. The remaining four paragraphs (lines 106-138) pertain to Methods, an essential part of Methods.

Figure 1 (lines 142, 163-5) should be replaced in Results. Just describing which were the variables collated in this study is enough for this segment of Methods. Depicting graphically the Results is a strength of the study. The maps provide a synthetical perception of the problem by region, state, and town. However, I missed a tabular display of cities and towns with higher or lower accessibility, maybe as a supplement. Such information would be critical to document the problem and guide solution attempts at the municipal level.

The figures have poor visual accuracy; they need a higher resolution. They also need a more explicative heading. Figure 1’s heading is meaningless. Figures 2-4’s headings are relatively interchangeable; I missed an unequivocal indication of which figure is showing accessibility by which criteria.

I observe that the North region had a higher number of snake accidents (Figure 5) and the most significant travel challenge (Figures 2-4). This remark is the study’s conclusion; it could not have been preliminarily stated in the Introduction (lines 92-4) without referring this information to the literature or to empirical data (which, of course, were subsequently reported).

I missed the acknowledgment of study limitations. The Discussion’s last paragraph pointed out the strength of having gathered an extensive, nationwide database. However, traveling to the health unit that offers sera is not the only interval to the treatment. In particular, the period from the casualty and the access to transport may result in a significant preliminary delay. This study cannot infer this matter, though this delay can enlarge the time to treatment. I suggest that the authors discuss this issue as a study limitation.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Jose Leopoldo Ferreira Antunes

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PLoS One. 2022 Jan 13;17(1):e0260326. doi: 10.1371/journal.pone.0260326.r002

Author response to Decision Letter 0


12 Aug 2021

Rio de Janeiro, August 12th, 2021

Rebuttal Letter

Dear editors and reviewers,

Thank you for the revision and suggestions to improve our manuscript. In order to resubmit it, we answer each one of the points that the academic editor and the reviewers raised about our work. First, we respond to the Journal Requirements and then to all the requests and suggestions, putting the points in italic and our answers just below.

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Maps at the CIA (public domain): https://www.cia.gov/library/publications/the-world-factbook/index.html and https://www.cia.gov/library/publications/cia-maps-publications/index.html

NASA Earth Observatory (public domain): http://earthobservatory.nasa.gov/

Landsat: http://landsat.visibleearth.nasa.gov/

USGS EROS (Earth Resources Observatory and Science (EROS) Center) (public domain): http://eros.usgs.gov/#

Natural Earth (public domain): http://www.naturalearthdata.com/

In order to solve the demand about copyrighted figures we decided to change the background of Figure 1 using the suggested USGS National Map Viewer (public domain): http://viewer.nationalmap.gov/viewer/. That figure was only on with Google Maps background. The other figures were built using Brazilian Institute of Geography and Statistics (IBGE – https://www.ibge.gov.br/apps/basescartograficas/) cartographic base, which have public domain and are available to reuse considering the metadata that follows ISO 19115 as standard. The figure captions were updated with this information.

Review Comments to the Author

Reviewer #1: Abstract

- Background must clearly describe the purpose of the study.

- Methods must describe: the type of study design and the method used (ACCESSMOD), the data collection and analysis, and the measures used in the description of Results, summarizing what was presented in the Methods section of the manuscript.

- In Results, the states that present the longest time to health units should be highlighted.

The abstract was updated considering the requests and suggestions, so the purpose of the study was included, the methods were more detailed and the States with more problems of accessibility were highlighted.

Background

- The paragraphs in lines 106-113 and 127-138 would be more suitable in the Methods section and not in the Background.

- The last paragraph of the Background should describe the purpose of the study.

The section was changed considering the need of reallocation of some paragraphs to Methods and the purpose of the study defines the last paragraph of the Introduction.

Methods

- The type of study design must be described in the first paragraph.

- After the subtitle and paragraph referring to “Distance calculation”, it is necessary to describe in detail the tabulation and data analysis process, as well as the measures which were used, statistical tests and the level of significance considered.

- The authors used 3 distinct geographic analysis units: macro-regions, federative units (states and Federal District) and municipalities. This should also be described in Methods.

The type of the study was included in the paragraph of the Methods section, which also had the inclusion of the three distinct geographic analysis units. The Distance Calculation subsection was updated with more information about the calculation process developed on ACCESSMOD, which considers Dijkstra least-cost path algorithm. This last information make reference to an article that presents the software:

Ray N, Ebener S. AccessMod 3.0: computing geographic coverage and accessibility to health care services using anisotropic movement of patients. Int J Health Geogr. 2008; https://doi.org/10.1186/1476-072X-7-63

Results

- In lines 277-285, I suggest that the calculation of the incidence rate be revised, since the indicator in the DF, São Paulo and Salvador has been presented as 0.05. It would be more appropriate to work with the indicator per 100,000 inhabitants.

The vast majority of Brazilian municipalities has less than 100,000 inhabitants, so we prefer to calculate the incidence rate per 1,000 to keep a more realistic comparison. According to the 2019 Population Estimates, presented by IBGE, 44% of the municipalities had less than 10,000 inhabitants and 94.2% had less than 100,000.

Discussion

It is important to discuss not only the innovation proposed by this study, but also its limitations, at the end of the section.

The limitations of the study were updated with more details and discussions. It is located at the penultimate paragraph of the Section.

Reviewer #2:

Snakebite accidents are, in some regions, relevant public health issues. The WHO's recognition, including this problem in the list of neglected tropical diseases, was an important step towards the production of more knowledge on the subject and, mainly, the mobilization of governments and other institutions to reduce the damage caused by this type of event. The manuscript has the merit of addressing this topic, which is of regional relevance in Brazil.

I understand that the central focus of the work and its strength are in the application of the method that analyzes the distance between health units and population distribution. As the author himself mentions, it could be used for other health situations. The problem is using this single analysis to base the entire discussion of the manuscript.The subject of snake accidents ends up being secondary and treated in a superficial way or weakly based on the results obtained from the performed analyses. Fundamental factors were left out or were superficially addressed, if we consider the endo f the title “Timely access possibilities.” For example, the availability of serum.

The manuscript ignores the limited availability of the serum and, therefore, assumes the existence of an unlimited amount of the product. It assumes that adequate allocation in health units would only lack evidence-based rationalization (the model presented, for example). Unfortunately, that's not the reality. The distribution of sera is fundamentally conditioned by its availability.

The WHO classification itself highlights this discussion. It is not just the affected population that defines an illness as neglected. The industry's insufficient investment as well. In the case of the production of serums, this is even more sensitive, since the production, usually, has to be regionalized according to the specificity of the snake species, with specific distribution.

To cope with these comments we try to amplify the characterization of the study as an analysis of geographical accessibility, not access or even use in fact of the services. To do so, a more theoretical paragraph about the complex concept of access and its dimensions, which includes geographical accessibility, was written in the Introduction. In addition, we have increased the limitation approach in the Discussion section in order to make clear that the actual availability of serum is not a subject of the manuscript, but has fundamental importance in the question.

The definition of snakebite accidents as neglected disease subsidizes our evaluation of the difficulties to access health facilities in terms of the location and the costs due the need of commuting, especially in regions with remote population and poor availability of transportation means and routes.

In Brazil, three public funded research institutions also produce antiophidic sera: Instituto Butantan (https://butantan.gov.br/), Fundação Ezequiel Dias (http://www.funed.mg.gov.br/) e Instituto Vital Brazil (http://www.vitalbrazil.rj.gov.br/index.html). Many authors consider that the production in our country is stable since the beginning of the 21st century as we include in the Discussion section. Obviously, this does not mean that there are no problems in production or distribution, but allows to a better situation when comparing to other developing countries.

Not every population more than two hours away from the health units that provide serum is under the same risk of snakebiting. The categorization of the most isolated populations in terms of risk would be essential to better qualify the analysis and enable a prioritization criterion to support decision-making and suggest “timely access possibilities” as the title says. Municipalities with higher incidences are briefly mentioned, but the discussion is not go further.

To deal with this comment we include more paragraphs at Results and Discussion’ sections. The characterization of risk was done considering geographical units with important incidence in 2019 and poor geographical accessibility to health facilities. We develop more paragraphs about the worst situations between Brazilian municipalities and include a Supplemental File with the municipalities with incidence rate in 2019 and population not covered in two-hour time. Our approach is related to the possibility of reach a facility that could provide antiophidic serum, hoping that it can be useful in planning process to expand the access to this network. Therefore, it is the possible access in opportune time that we analyse.

Furthermore, the quality of the information is not discussed. For example, when commenting on the large number of cases in the city of São Paulo, the author mentions only the large population of the city as an explanation and does not assess the possible effect on the notifications of the existence of very important references (regional and national) in the treatment of snakebite accidents, located in its territory.

We include comments and references about the quality of information about snakebite accidents in a new subsection created in Methods. The information we use refers to place of residence, so the effect of health care references is reduced, but for sure there is a possibility of better notification in some regions and we pointed it in the text. There is a lack of more recent studies about the quality of the information about snakebite accidents on SINAN.

For these reasons, it seems a little ambitious to discuss "timely access possibilities", based almost exclusively on the distance between the population and the health unit, without analyzing risk, serum availability, health system configuration, information quality.

We consider the timely access possibilities from the perspective of geographical accessibility to health facilities. It does not mean that we consider our approach as sufficient to deal with all the complexities of the question, we understand its limitations, but we think even so is a relevant contribution to public policies in this subject.

There are some problems with the references. For example, information on the WHO classification of snakebites as a neglected tropical disease is referenced to the article "Longbottom J, Shearer FM, Devine M, Alcoba G, Chappuis F, Weiss DJ, Williams, DJ. Vulnerability to snakebite envenoming: A global mapping of hotspots. The Lancet. 2018; 392(10148): 673-84". However, the information is not from this article, which cites original information from WHO document "Report of the tenth meeting of the WHO Strategic and Technical Advisory Group for neglected tropical diseases. World Health Organization, Geneva2017".

The WHO report was included in the References of the manuscript.

In my opinion, the work presented allows discussing only the geographic distribution of the population in relation to the units that provide serum, without assuming that this analysis is sufficient to think about strategies for expanding access to services.

We do not think that this is sufficient to think about strategies to expand access to health services, but we think it as a contribution to the academic debate and to the planning process.

Reviewer #3:

This manuscript assessed the accessibility to antiophidic sera in the Brazilian context. Snakebite accidents are a neglected public health problem in the country; the knowledge aimed at by the present study is certainly relevant to health policy and planning in many remote and rural areas. The text is well written and can be read smoothly. However, it is poorly organized.

The Introduction is unnecessarily too large. It should have ended in line 97, after stating the study objective. Using different geographical areas (lines 97-8) in the approach is related to Methods, not the Introduction. That this analysis allows discussing accessibility to other health services (lines 99-105) is a matter for Discussion. The remaining four paragraphs (lines 106-138) pertain to Methods, an essential part of Methods.

In order to deal with the perception of poor organization, we made some changes in the manuscript. The Introduction was reduced with the transference of parts to Methods and to the Discussion section, just as suggested.

Figure 1 (lines 142, 163-5) should be replaced in Results. Just describing which were the variables collated in this study is enough for this segment of Methods.

Agreeing with this suggestion, Figure 1 was replaced in Results, with the inclusion of a paragraph where some comments about it were included.

Depicting graphically the Results is a strength of the study. The maps provide a synthetical perception of the problem by region, state, and town. However, I missed a tabular display of cities and towns with higher or lower accessibility, maybe as a supplement. Such information would be critical to document the problem and guide solution attempts at the municipal level.

Considering the relevance of such suggestion, a tabular display of the municipalities with incidence rate in 2019 and population not covered in two-hour time was included in the submission as Supplemental File. We believe that can published as .csv or even a text document. Additionally, other comments about the question were included in the Discussion.

The figures have poor visual accuracy; they need a higher resolution. They also need a more explicative heading. Figure 1’s heading is meaningless. Figures 2-4’s headings are relatively interchangeable; I missed an unequivocal indication of which figure is showing accessibility by which criteria.

A higher resolution would increase the file size, so it is not possible to replace them. To cope with demand of improving the headings, we change those from Figures 1, 3 and 4, with intent to clarify its content. Figure 2-4 registers the accessibility of population of defined geographic units that can access serum providing health facilities in two-hour time. However, while Figure 2 register the distribution of the reaching coverage, Figures 3 and 4 registers the share of population with possibility to reach the considered health facilities, by States (Fig 3) and by municipalities (Fig 4).

I observe that the North region had a higher number of snake accidents (Figure 5) and the most significant travel challenge (Figures 2-4). This remark is the study’s conclusion; it could not have been preliminarily stated in the Introduction (lines 92-4) without referring this information to the literature or to empirical data (which, of course, were subsequently reported).

Agreeing with this suggestion, all the comments about the relevance of the question at the North region were transferred to Discussion section.

I missed the acknowledgment of study limitations. The Discussion’s last paragraph pointed out the strength of having gathered an extensive, nationwide database. However, traveling to the health unit that offers sera is not the only interval to the treatment. In particular, the period from the casualty and the access to transport may result in a significant preliminary delay. This study cannot infer this matter, though this delay can enlarge the time to treatment. I suggest that the authors discuss this issue as a study limitation.

The study limitations were updated with more details and discussion, including the question of the time between the snakebite accident and the actual access to transportation.

Kind regards,

Ricardo Antunes Dantas de Oliveira, Diego Ricardo Xavier Silva and Maurício Gonçalves e Silva

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 1

Ahmed Mancy Mosa

6 Oct 2021

PONE-D-21-22192R1Geographical accessibility to the supply of antiophidic sera in Brazil: Timely access possibilitiesPLOS ONE

Dear Dr. Oliveira,

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

PLOS ONE

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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.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

Reviewer #3: 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

Reviewer #3: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: N/A

Reviewer #3: Yes

**********

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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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: Abstract

- Methods must describe: the type of study design.

Methods

- Data analysis: it is necessary to describe, as well as the association measures which were used, the statistical tests and the level of significance considered.

Reviewer #2: I'd like to thank all the authors for their answers. The theme is relevant to public health, especially because it affects more seriously socially vulnerable communities. I have no further comments.

Reviewer #3: (No Response)

**********

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Jose Leopoldo Ferreira Antunes

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Attachment

Submitted filename: Review October1st.pdf

PLoS One. 2022 Jan 13;17(1):e0260326. doi: 10.1371/journal.pone.0260326.r004

Author response to Decision Letter 1


22 Oct 2021

Dear editors and reviewers,

Thank you for the revision and suggestions to improve our manuscript. In order to resubmit it, we answer the points that the academic editor and one of the reviewers raised about our work. First, we respond to the Journal Requirements and then to the requests and suggestions, putting the points in italic and our answers just below.

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.

The reference list was reviewed in order to correct it, considering the reference style of International Committee of Medical Journal Editors (ICMJE). As a new reference was included, the reference indications were changed in the text and also the reference list.

Review Comments to the Author

Reviewer #1: Abstract

Methods must describe: the type of study design.

The abstract was updated considering the request, adding the type of study design.

Methods

Data analysis: it is necessary to describe, as well as the association measures which were used, the statistical tests and the level of significance considered.

In order to improve the information about the travelling time calculation, the first paragraph of the Methods section was changed. Also, a new reference was included, to better characterize the algorithm considered in ACCESSMOD 5.0, the software which was used to estimate traveling time to health facilities. The Distance and time to reach health facilities calculation subsection was altered in order to include this information.

There is no other information about the association measures which were used, the statistical tests and the level of significance considered, because we do not use specific statistical analysis and even other authors that use the software do not bring those details. But the referred new article can provide a more detailed information about the travel time cost surface model.

Dijkstra, E.W. A note on two problems in connexion with graphs. Numer. Math. 1959;1: 269–271. https://doi.org/10.1007/BF01386390

Kind regards,

Ricardo Antunes Dantas de Oliveira, Diego Ricardo Xavier Silva and Maurício Gonçalves e Silva

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 2

Ahmed Mancy Mosa

8 Nov 2021

Geographical accessibility to the supply of antiophidic sera in Brazil: Timely access possibilities

PONE-D-21-22192R2

Dear Dr. Oliveira,

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,

Ahmed Mancy Mosa, Ph.D.

Academic Editor

PLOS ONE

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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

**********

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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

**********

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

Reviewer #1: 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

**********

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Reviewer #1: Yes

**********

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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: (No Response)

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Reviewer #1: No

Acceptance letter

Ahmed Mancy Mosa

4 Jan 2022

PONE-D-21-22192R2

Geographical accessibility to the supply of antiophidic sera in Brazil: Timely access possibilities

Dear Dr. Oliveira:

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.

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on behalf of

Dr. Ahmed Mancy Mosa

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 Appendix. Snakebite accidents, population, incidence rate and uncovered population (%) by Brazilian municipalities, 2019.

    (DOCX)

    Attachment

    Submitted filename: Response to Reviewers.docx

    Attachment

    Submitted filename: Review October1st.pdf

    Attachment

    Submitted filename: Response to Reviewers.docx

    Data Availability Statement

    The datasets and basic map generated during the study development is available with no restriction at https://doi.org/10.7303/syn26042133. The Snakebite accidents data that support the findings of this study are available from SINAN - Notifiable Diseases Information System, at http://www2.datasus.gov.br/DATASUS/index.php?area=0203&id=29878153. The Statistical Grid data that support the findings of this study are available in IBGE - Brazilian Institute of Geography and Statistics, at https://portaldemapas.ibge.gov.br/portal.php#homepage. The road network and land use data that support the findings of this study are available from OPEN STREET MAP (OSM), at: https://www.openstreetmap.org/. The Digital Elevation Model data that support the findings of this study are available from Earth Data - Open Access for Open Science, at: https://earthdata.nasa.gov/eosdis/daacs/lpdaac. The health facilities data that support the findings of this study are available from CNES - National Register of Health Facilities, at http://www2.datasus.gov.br/DATASUS/index.php?area=0204&id=6906 The 2019 population estimates data that support the findings of this study are available in IBGE - Brazilian Institute of Geography and Statistics, at https://www.ibge.gov.br/estatisticas/sociais/populacao/9103-estimativas-de-populacao.html?=&t=o-que-e.


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