Predictor Variables in the Spread of Chagas Disease in Rural Areas

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Thank you for the opportunity to review the manuscript titled "Predictor variables in the dissemination of the Chagas Disease in rural areas.” Overall, this is an extensive and well- addressed review that systematically analyzes variables influencing the spread of Chagas disease. There are, however, some areas that could be improved to better communicate the findings:

While it’s conducted a quantitative analysis of variables found in the literature, presenting this information through graphs and tables would help readers more easily understand the relationships identified. Graphically representing factors like the frequency and level of association of different variables with disease prevalence would strengthen the presentation of results.

The length and detail provided in the written description make it challenging to extract the most important conclusions. Shortening and restructuring the text focused on the key variables could help address this. Prioritizing 2-3 primary variables identified as influencing spread based on a quantitative analysis of their prevalence and strength of correlation in the studies would be valuable.

Similarly, directly comparing the percentages mentioned in the text using statistical measures would allow weighting the relative contribution of different variables. This type of quantitative prioritization is missing from the current analysis.

One minor comment - The description incorrectly states that Mexico is located in Central America on multiple occasions within the writing (line 47, 63, 64, 201 and 202). However, Mexico is situated in North America. The repetition of "in" (line 22) at the end of the abstract summary is a typo that should be removed.

Overall, this study provides a comprehensive overview of the literature on Chagas disease determinants. Incorporating graphical representation of quantitative results and focusing the length and structure on top conclusions drawn would enhance communication of the important findings.

Author Response

Dear Revisor

We thank the reviewer for the corrections and suggestions for improvements in our article. We hope we have addressed them all!

We are available for any further clarifications.

 

Revisor 1

Comments and Suggestions for Authors

Thank you for the opportunity to review the manuscript titled "Predictor variables in the dissemination of the Chagas Disease in rural areas.” Overall, this is an extensive and well- addressed review that systematically analyzes variables influencing the spread of Chagas disease. There are, however, some areas that could be improved to better communicate the findings:

 

While it’s conducted a quantitative analysis of variables found in the literature, presenting this information through graphs and tables would help readers more easily understand the relationships identified. Graphically representing factors like the frequency and level of association of different variables with disease prevalence would strengthen the presentation of results.

Answer: Graphs and figures were created to better explain the findings of the research. I hope we have met your expectations.

 

The length and detail provided in the written description make it challenging to extract the most important conclusions. Shortening and restructuring the text focused on the key variables could help address this. Prioritizing 2-3 primary variables identified as influencing spread based on a quantitative analysis of their prevalence and strength of correlation in the studies would be valuable.

Answer: We chose to leave all variables, but we described some that were more evident in the forest plot. I hope this approach is acceptable

 

Similarly, directly comparing the percentages mentioned in the text using statistical measures would allow weighting the relative contribution of different variables. This type of quantitative prioritization is missing from the current analysis.

Answer: Changes have been made throughout the text in an effort to meet the request.

 

One minor comment - The description incorrectly states that Mexico is located in Central America on multiple occasions within the writing (line 47, 63, 64, 201 and 202). However, Mexico is situated in North America. The repetition of "in" (line 22) at the end of the abstract summary is a typo that should be removed.

Answer: It was a big mistake on our part. The information has been corrected.

 

Overall, this study provides a comprehensive overview of the literature on Chagas disease determinants. Incorporating graphical representation of quantitative results and focusing the length and structure on top conclusions drawn would enhance communication of the important findings.

Answer: We believe we have met the requests/recommendations.

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

Predictor variables in the dissemination of the Chagas Disease in rural areas

 

This study presents an interesting review of Chagas Disease, trying to organize practical knowledge for the implementation of disease prevention programs in rural environments. In recent times, however, I have observed that there is a high frequency of review studies in many thematic fields. Although I recognize the need to carry out compendiums and organizations of previous studies, I encourage all the authors who carried out them to also undertake field studies, which help to improve the existing gaps in knowledge, and specifically about Chagas Diseases.

 

Particularly, I think this study is very interesting and important, but I consider it to be excessively long. In my opinion, the authors should reflect on how to make the manuscript more dynamic, clear and less redundant. Basically, I recommend:

·       Simplify long sentences. Sentences of four lines or more than two verbs are already very long.

·       Although agree with the methodology and the way the article is constructed, I think that the authors should be more global when making the discussion and not explain the details of specific studies. The article is too long (32 pages and simple space), and, in my opinion, should be much more dynamic. The details of most of the studies do not provide significant information. As it is now the article is too long, and I think it should be reduced by 33% (approx. of course); thus, author should select the information, and eliminate details that slow down the reading.

 

Minor comments

 

Abstract:

L22: “in in environments”

Could the authors highlight the most frequently significant factors?

 

Introduction

I think the introduction should be ordered. Parts of the introduction are interspersed and should be ordered to improve understanding. The main parts presented are: geographical distribution of the disease, epidemiology and pathogenicity, and rurality of CD. The first two are interspersed and need to be clearer and more organized.

 

In the whole document: Delete “The” within “The Trypanosoma cruzi”

 

Likewise, throughout the document, I suggest simplifying the sentences and not constructing long sentences, which tend to make understanding difficult. For example, no sentences with more than 3 lines.

 

L36-39. Break sentences for better understanding: “In the transmission cycle, the triatomine becomes a vector by feeding on mammalian blood contaminated by T. cruzi, where it multiplies and acquires the infectious flagellated trypomastigote. Due to defecating after biting, the protozoan is transmitted to humans or other vertebrate mammals by scratching the skin with feces.” Also, explain the role of skin scratching in the transmission.

 

L40-43. I recommend dividing the “Other forms of transmission” into two groups, on the one hand: “transplacental, transfusion or organ transplantations, laboratorial accidents and sexual transmission”, and, on the other hand oral route, since they are clearly different. Also, the oral route is especially important in rural environments. By this way, the context and knowledge of this oral route could be expanded a little more.

 

L44-46. Since Southern and Central America is Hispanic and Portuguese-speaking, I recommend completing the common triatomine terminology with Spanish vocabularies.

 

L49-52. Break the sentence to improve your understanding. It may be appropriate to briefly explain why migratory movements are important. That will link to the next sentence.

 

Authors have defined the distribution range of the vector, but perhaps they should connect it to the distribution range of CD, as the concept of migration and spread of the disease is introduced. Here the conceptual set could be explained. Therefore connect both paragraphs.

 

L56-57: “Chagas disease is found in the north of the American continent [16,17], the European continent [15], the East [13] and in 21 Latin American countries [3,12,18].”. Why do the 21 Latin American countries stand out and not countries from other regions? All this is connected to the previous concept of the natural distribution range of the disease and immigrations. Therefore, I think it is important to explain the entire concept in a unitary way.

 

However, much importance is given to the territorial range, trying to provide prevalence data in some cases, but not in all cases. That results in unequal information. Try to homogenize the information by region. On the other hand, make it more general since the topic of study is CD in rural areas.

 

L103-108. This paragraph presents epidemiological data, other data in the same epidemiological context have been placed in previous paragraphs. I suggest putting all these data together in the same paragraph since it will complete the idea of ​​the importance (severity) of the disease. In this way, I think the Introduction will be better organized.

 

L107-112. Change: “It is essential to know the risk variables of CD dissemination, observe its forms of transmission, to base strategies for its control and prevention. This work aimed to identify predictor variables that explain the dissemination of Trypanosoma cruzi infection in humans in rural areas.”

 

Material and Methods

Appropriate systematic method of inclusion or exclusion of articles. However, I always recommend, in addition, that an additional parallel search effort be made with other keys, because sometimes some interesting articles escape or because the researchers themselves know (due to their expertise) other works. Therefore, complete the systematic method unsystematically, to improve the effort of collecting articles.

 

L115-116. Why is this phrase italicized?

 

The natural geographical distribution range of CD is Latin America, and we know that there are local groups that do not publish in English scientific journals, even though these are good studies (both in Portuguese and Spanish-speaking areas), in this way, I suggest including a methodological step in which this effort is made, so as not to exclude works of valuable contribution. We always have an important bias because there are codes of considering “scientific” only science written in English. Considering this is a major unforeseen effort, I leave the decision in the hands of the authors, as they have done a good job so far.

 

MS Office programs are not referenceable programs. There is no need to mention them as they are very standard.

 

Results and Discussion

L190-197. Delete or reduce the entire paragraph to a conclusion “85 have been used for the identification of predictor variables and influencers of CD”, all the paragraph is redundant with Figure 2

 

L201-202: “The analyzed works have been mainly developed in Latin America: Brazil (24.7%), Argentina (22.4%), Mexico (16.5%), Venezuela (12.9%), Colombia (5.9%), Peru, Chile, Ecuador, Bolivia, Guatemala, Nicaragua, Panamá, Paraguay and Uruguay (<3.5%) (Graphic 1). Studies with Latino-American immigrants (2.4%) has also been conducted in Spain.”. The Graph is not necessary, it repeats information.

 

L204-206. “However, within this universe, the search and presence of the vector has been seen in 28.2% of the articles (24/85), in seven countries: Argentina, Brazil, Chile, Mexico, Panama, Peru and Venezuela, as posteriorly observed in the item of the housing variable referring 206 to the presence of triatomines in households.” If this is a selection criterion, it is not necessary to mention it. Just describe the result later. I suggest deleting this paragraph.

 

L210. “It was possible to determine that”. These types of expressions should be deleted.

 

L210: “The 64.7% of the studies have been developed also in rural areas; however, almost 35% of the studies have been developed also in urban and periurban areas, being: urban and rural (29.4%); urban, periurban and rural (3.5%); and periurban and rural (2.4%) areas.” I always recommend ordering in decreasing percentages.

 

L212-221. I think is important to improve the way information is presented. It is necessary to make more and shorter sentences to ensure the transmission of clear messages. This must be done throughout the document.

 

L221. Explain the relationship with nocturnal habits, now I don't understand well. “once that they are wild or domiciled insects of nocturnal habits”

 

L223-226. The article is quite long. Is this information esential?

 

L226-230. Include in M&M

 

L232-234. “After analyzing the articles contents, 27 variables were obtained (Table 1), being 19 independent predictors and 8 dependent predictors for the dissemination of CD, which, according to their applicability of possible improvement actions, mainly in the rural area, 234 have been organized in groups characterized by prediction and dependence (Table 1).” Again, break the sentence into two sentences.

 

Table 1. I invite authors to design a more visual Table (or Figure). On the other hand, I believe that the subtitles of the “Results and discussion” section should be displayed in the Table to improve the synthetic vision, and, in addition, place frequencies of occurrence of significant factors.

 

L253-257. I think this paragraph does not provide substantial information.

 

All Figures and Tables. I think it is not necessary to put “Source: own creation”. I understand that reference should be made to figures and tables that do NOT belong to the authors. The manuscript already has the signature of the authors.

 

L275-292. It's a too large introduction; please, reduce this paragraph.

 

L295. CURRENT RESIDENCE LOCATION, Delete CURRENT

 

L315-318. It is not necessary to specify the place, unless here (and not in other studies) it is especially important.

 

L318-324. “Besides that, the authors identified that the household in urban area resulted in a protection factor against CD (OR=0.34), which contrasts with the research conducted in rural and urban indigenous communities in Argentina, in which was found that the CD prevalence in the urban indigenous community was 6,4 times higher than in the rural community [55]. According to the authors, the process of indigenous rural exodus is recent and undergone by individuals which, in their place of origin, lived in precarious socio-sanitary conditions.” Is this the only study where the probability in areas is higher? It would be interesting to explain it clearly. In the explanation given I do not understand the explanation clearly: “According to the authors, the process of indigenous rural exodus is recent and undergone by individuals which, in their place 323 of origin, lived in precarious socio-sanitary conditions.”

 

The case of Venezuela is consistent with the rest of the studies. Why is it highlighted here?

 

L325-333. Authors should include a briefer and more global explanation, without describing the specific cases in such detail. The reviews do not have to discuss all the studies, but rather build a synthetic and globalizing knowledge. Only highlight specific issues when essential. “The studies of this universe which consider as current residence location, the geographical location and areas vulnerabilities, observed: among 18 rural communities in the state of Piauí, Brazil, significant difference (p<0.001) due to house improvements resulting from intervention programs ([28]; between two Brazilian municipalities, significant difference (p<0.001) justified in reports of coexistence with triatomines in the household ([65]; and between state regions, observing that the geographical and climatologic characteristics of the western region of Sucre, in Venezuela, with coffee tree regions and big climate variation, made the chance of T. cruzi infection 7,4 times greater for the local population in relation to the other regions (p<0.05; OR=7.4) [64].”

 

L339-358. Again, authors should build the concept without including specific details. Be careful! with the concept of “unskilled”, this type of concept makes sense in cities, in rural areas, I would ask why extracting açai or being a hunter is a non-qualified job? I am a scientist and I am not qualified to hunt. Perhaps it is important to talk about “formalized work”

 

L359. Be careful!. FORMAL EDUCATION. Rural education especially should be differentiated in planned education by the states (formal) and informal education, more practical, enhanced by families and based on domestic (and rural) activity. If the authors even intend to partially define the concept, they must give a more global, and not just urban, definition of education.

 

Formal education is probably related to rurality and/or location of residence? It was already explained in reverse. That is because there are interdependent factors that at some point in the study I think should be explained and addressed.

 

L368-379; L389-405; L416-432; L441-442; L254-261; L477-531, L550-555; L569-576; L585-603; L605-611 AND SO ON… The same with concrete studies, draw global conclusions, place only the essentially different and important cases; and finally, if necessary, build a Suppl Table displaying these summarized details

 

Changes subtitles:

·       ACCUMULATION OF WOOD/FIREWOOD IN THE PERIDOMICILE included within PERIDOMICILIARY STRUCTURES BUILDING MATERIAL

·       PRESENCE OF INFECTED OR NON-INFECTED TRIATOMINES IN THE HOUSEHOLDS = TRIATOMINES IN THE HOUSEHOLDS

·       PRESENCE OF DOMESTIC ANIMALS IN THE HOUSEHOLDS, INFECTED OR NOT = DOMESTIC ANIMALS IN THE HOUSEHOLDS

·       PRESENCE OF SINANTROPIC AND/OR WILD ANIMALS IN THE HOUSEHOLDS, INFECTED OR NOT = SINANTROPIC AND/OR WILD ANIMALS IN THE HOUSEHOLDS

·       PRESENCE OF HUMAN HOST WITH CD = HUMANS WITH CHAGAS DISEASE

·       DENSIFICATION OF PEOPLE IN THE INTRADOMICILE = INTRADOMICILIAR HUMAN DENSITY

 

Final Considerations

I would begin this section with the presentation of “collinearity” or interdependence of a large part (or almost all) of the sociocultural and economic factors.

 

Conclusions

I think the authors should construct more synthetic conclusions, reduce their number, and do not repeat concepts from different sections. The most global conclusion is the last one. Finally, I think it is important to contextualize the value of the results within next steps in improving the disease, and/or include further studies needed.

 

 

Author Response

Dear Revisor

We thank the reviewer for the corrections and suggestions for improvements in our article. We hope we have addressed them all!

We are available for any further clarifications.

 

Comments and Suggestions for Authors

Predictor variables in the dissemination of the Chagas Disease in rural areas

 

This study presents an interesting review of Chagas Disease, trying to organize practical knowledge for the implementation of disease prevention programs in rural environments. In recent times, however, I have observed that there is a high frequency of review studies in many thematic fields. Although I recognize the need to carry out compendiums and organizations of previous studies, I encourage all the authors who carried out them to also undertake field studies, which help to improve the existing gaps in knowledge, and specifically about Chagas Diseases.

 

Particularly, I think this study is very interesting and important, but I consider it to be excessively long. In my opinion, the authors should reflect on how to make the manuscript more dynamic, clear and less redundant. Basically, I recommend:

• Simplify long sentences. Sentences of four lines or more than two verbs are already very long.

Answer: recommendation fulfilled

• Although agree with the methodology and the way the article is constructed, I think that the authors should be more global when making the discussion and not explain the details of specific studies. The article is too long (32 pages and simple space), and, in my opinion, should be much more dynamic. The details of most of the studies do not provide significant information. As it is now the article is too long, and I think it should be reduced by 33% (approx. of course); thus, author should select the information, and eliminate details that slow down the reading.

Answer: As recommended, the text has been adjusted, removing parts of the text and including graphs and figures for better understanding. Despite the inclusion of new information, the text still spans the same 32 pages, with 8 pages dedicated to references.

Abstract:

L22: “in in environments”

Could the authors highlight the most frequently significant factors?

Answer: recommendation fulfilled

 

Introduction

I think the introduction should be ordered. Parts of the introduction are interspersed and should be ordered to improve understanding. The main parts presented are: geographical distribution of the disease, epidemiology and pathogenicity, and rurality of CD. The first two are interspersed and need to be clearer and more organized.

Answer: recommendation fulfilled

 

In the whole document: Delete “The” within “The Trypanosoma cruzi”

Answer: the term “the” before T. cruzi was removed

 

Likewise, throughout the document, I suggest simplifying the sentences and not constructing long sentences, which tend to make understanding difficult. For example, no sentences with more than 3 lines.

Answer: Thank you for the suggestion. We undersatand it readability and comprehension, so we have made the changes as much as possible.

 

L36-39. Break sentences for better understanding: “In the transmission cycle, the triatomine becomes a vector by feeding on mammalian blood contaminated by T. cruzi, where it multiplies and acquires the infectious flagellated trypomastigote. Due to defecating after biting, the protozoan is transmitted to humans or other vertebrate mammals by scratching the skin with feces.” Also, explain the role of skin scratching in the transmission.

Answer: The text has been improved as suggested. In the transmission cycle, the triatomine becomes a vector after feeding on mammalian blood contaminated by T. cruzi [5]. Within its intestine, the protozoan multiplies and assumes the infective flagellated trypomastigote form [4]. Due to the insect's habit of defecating after biting, it transmits the protozoan T. cruzi to humans or other vertebrate mammals. This occurs when the skin is scratched, introducing the invertebrate's feces into the vertebrate's bloodstream at the site of the bite [4,5].

 

L40-43. I recommend dividing the “Other forms of transmission” into two groups, on the one hand: “transplacental, transfusion or organ transplantations, laboratorial accidents and sexual transmission”, and, on the other hand oral route, since they are clearly different. Also, the oral route is especially important in rural environments. By this way, the context and knowledge of this oral route could be expanded a little more.

Answer: Other forms of transmission include transplacental transmission and, more rarely, through blood transfusion or organ transplantations, laboratory accidents, and sexual transmission. Additionally, transmission can occur orally, mainly the ingestion of food contaminated with T. cruzi, which is related to the acute Chagas disease (ACD) [5,6].

 

L44-46. Since Southern and Central America is Hispanic and Portuguese-speaking, I recommend completing the common triatomine terminology with Spanish vocabularies.

Answer: The text has been improved as suggested. The CD vector, arthropod of the Triatominae (Hemiptera, Reduviidae) subfamily, also known as the kissing bug, conenose bug or vampire bug. In Brazil, it is referred to as “barbeiro, chupão, procotó, bicudo or chipó”, while in Hispanic countries, it goes by “barber, chuoetón, protocó bicudo or chipos”. This hematophagous insect exhibits nocturnal behavior [5,7,8] and is predominantly found in South and Central Americas. Some species also inhabit regions of the of the USA, center-southern Africa, southeastern Asia and northern Australia [5,7,9].

 

L49-52. Break the sentence to improve your understanding. It may be appropriate to briefly explain why migratory movements are important. That will link to the next sentence.

Answer: Adjustments were made to the text, changing the sequence, so we hope to have met the request.

 

Authors have defined the distribution range of the vector, but perhaps they should connect it to the distribution range of CD, as the concept of migration and spread of the disease is introduced. Here the conceptual set could be explained. Therefore connect both paragraphs.

Answer: We believe that with the adjustments in the sequence of the text, this issue has been resolved. Otherwise, we can make further changes.

 

L56-57: “Chagas disease is found in the north of the American continent [16,17], the European continent [15], the East [13] and in 21 Latin American countries [3,12,18].”. Why do the 21 Latin American countries stand out and not countries from other regions? All this is connected to the previous concept of the natural distribution range of the disease and immigrations. Therefore, I think it is important to explain the entire concept in a unitary way.

Answer: We believe that with the adjustments in the sequence of the text, this issue has been resolved. Otherwise, we can make further changes.

 

However, much importance is given to the territorial range, trying to provide prevalence data in some cases, but not in all cases. That results in unequal information. Try to homogenize the information by region. On the other hand, make it more general since the topic of study is CD in rural areas.

Answer: We believe that with the adjustments in the sequence of the text, this issue has been resolved. Otherwise, we can make further changes.

 

L103-108. This paragraph presents epidemiological data, other data in the same epidemiological context have been placed in previous paragraphs. I suggest putting all these data together in the same paragraph since it will complete the idea of ​​the importance (severity) of the disease. In this way, I think the Introduction will be better organized.

Answer: the paragraph did indeed appear out of place; it has since been relocated

 

L107-112. Change: “It is essential to know the risk variables of CD dissemination, observe its forms of transmission, to base strategies for its control and prevention. This work aimed to identify predictor variables that explain the dissemination of Trypanosoma cruzi infection in humans in rural areas.”

Answer: we appreciate the suggestion, which has been addressed

 

Material and Methods

Appropriate systematic method of inclusion or exclusion of articles. However, I always recommend, in addition, that an additional parallel search effort be made with other keys, because sometimes some interesting articles escape or because the researchers themselves know (due to their expertise) other works. Therefore, complete the systematic method unsystematically, to improve the effort of collecting articles.

Answer: An additional search for papers would require an extra effort that is currently not feasible. This study aimed to identify predictor variables that explain the spread of Trypanosoma cruzi infection in humans in rural areas, and we believe it has fulfilled its purpose. Therefore, we kindly ask the esteemed reviewer to understand the challenges and allow the continuation in its current form..

 

L115-116. Why is this phrase italicized?

Answer: The italic formatting has been removed.

 

The natural geographical distribution range of CD is Latin America, and we know that there are local groups that do not publish in English scientific journals, even though these are good studies (both in Portuguese and Spanish-speaking areas), in this way, I suggest including a methodological step in which this effort is made, so as not to exclude works of valuable contribution. We always have an important bias because there are codes of considering “scientific” only science written in English. Considering this is a major unforeseen effort, I leave the decision in the hands of the authors, as they have done a good job so far.

Answer: We understand and agree that additional search could contribute to improving the work. However, a search of this magnitude would require a lot of time, which is currently unfeasible.

 

MS Office programs are not referenceable programs. There is no need to mention them as they are very standard.

Answer: changed to an electronic spreadsheet format, and removed “in MS Office Powerpoint 2019”

 

Results and Discussion

L190-197. Delete or reduce the entire paragraph to a conclusion “85 have been used for the identification of predictor variables and influencers of CD”, all the paragraph is redundant with Figure 2

Answer: removed.

 

L201-202: “The analyzed works have been mainly developed in Latin America: Brazil (24.7%), Argentina (22.4%), Mexico (16.5%), Venezuela (12.9%), Colombia (5.9%), Peru, Chile, Ecuador, Bolivia, Guatemala, Nicaragua, Panamá, Paraguay and Uruguay (<3.5%) (Graphic 1). Studies with Latino-American immigrants (2.4%) has also been conducted in Spain.”. The Graph is not necessary, it repeats information.

Answer: We accepted the suggestion and removed the graph.

 

L204-206. “However, within this universe, the search and presence of the vector has been seen in 28.2% of the articles (24/85), in seven countries: Argentina, Brazil, Chile, Mexico, Panama, Peru and Venezuela, as posteriorly observed in the item of the housing variable referring 206 to the presence of triatomines in households.” If this is a selection criterion, it is not necessary to mention it. Just describe the result later. I suggest deleting this paragraph.

Answer: The presence of the triatomine was not a selection criterion, so we believe the sentence should remain.

 

L210. “It was possible to determine that”. These types of expressions should be deleted.

Answer: ok

 

L210: “The 64.7% of the studies have been developed also in rural areas; however, almost 35% of the studies have been developed also in urban and periurban areas, being: urban and rural (29.4%); urban, periurban and rural (3.5%); and periurban and rural (2.4%) areas.” I always recommend ordering in decreasing percentages.

Answer: Changed to Among the studies, 64.7% have been developed also in rural areas. However, nearly 35% of the studies have also been conducted in urban and periurban areas, including: urban and rural (29.4%); urban, periurban and rural (3.5%); and periurban and rural (2.4%) areas.

 

L212-221. I think is important to improve the way information is presented. It is necessary to make more and shorter sentences to ensure the transmission of clear messages. This must be done throughout the document.

Answer: ok => Despite rural areas remining a cause for concern due to the critical social conditions of certain regions associated with poverty, leading to precarious living conditions [54], the urbanization of Chagas disease has increasingly become a subject of study for similar reasons. This phenomenon prompts migratory movements in search of improved living conditions [55-57].

 

L221. Explain the relationship with nocturnal habits, now I don't understand well. “once that they are wild or domiciled insects of nocturnal habits”

Answer: Text changed to:  For example, between Red Cross blood donors, in the USA, infected individuals have been identified. These individuals have resided in precarious households and/or rural areas, and despite living in urban area, performed nocturnal leisure or work activities in forested areas of the regions with documented report of existence of triatomines and animals host for T. cruzi [20], thereby increasing the likelihood of contact with triatomines. This is due to the fact that triatomines are wild or domiciled insects with nocturnal habits [7].

 

L223-226. The article is quite long. Is this information esential?

Answwer: removed. The analyzed articles have presented methodologies with descriptive analysis in field research (16.55%, 14/85) and statistical analysis (83.5%, 71/85), with the predominant use of the statistical tools Test X² (Chi-squared test) in 56.3% (40/71) and Odds Ratio (OR) in 26.8% (19/71).

 

L226-230. Include in M&M

Answer: Text changed

 

L232-234. “After analyzing the articles contents, 27 variables were obtained (Table 1), being 19 independent predictors and 8 dependent predictors for the dissemination of CD, which, according to their applicability of possible improvement actions, mainly in the rural area, 234 have been organized in groups characterized by prediction and dependence (Table 1).” Again, break the sentence into two sentences.

Answer: Text changed to “After analyzing the articles contents, 27 variables were obtained (Graphic 1): being 19 independent predictors and 8 dependent predictors for the dissemination of CD. Have been organized in groups characterized by prediction and dependence, which, according to their applicability of possible improvement actions, mainly in the rural área (Graphic 1).”

 

Table 1. I invite authors to design a more visual Table (or Figure). On the other hand, I believe that the subtitles of the “Results and discussion” section should be displayed in the Table to improve the synthetic vision, and, in addition, place frequencies of occurrence of significant factors.

Answer: The table was transformed into a graph, including the articles found, as well as those with significant values.

  

L253-257. I think this paragraph does not provide substantial information.

Answer: We accepted the suggestion and removed the text.

 

All Figures and Tables. I think it is not necessary to put “Source: own creation”. I understand that reference should be made to figures and tables that do NOT belong to the authors. The manuscript already has the signature of the authors.

Answer: all of them have been removed

 

L275-292. It's a too large introduction; please, reduce this paragraph.

Answer: The text was redistributed to before Graphic 1 and to the final considerations.

 

L295. CURRENT RESIDENCE LOCATION, Delete CURRENT

Answwer: ok removed.

 

L315-318. It is not necessary to specify the place, unless here (and not in other studies) it is especially important.

Answwer: ok removed.

 

L318-324. “Besides that, the authors identified that the household in urban area resulted in a protection factor against CD (OR=0.34), which contrasts with the research conducted in rural and urban indigenous communities in Argentina, in which was found that the CD prevalence in the urban indigenous community was 6,4 times higher than in the rural community [55]. According to the authors, the process of indigenous rural exodus is recent and undergone by individuals which, in their place of origin, lived in precarious socio-sanitary conditions.” Is this the only study where the probability in areas is higher? It would be interesting to explain it clearly. In the explanation given I do not understand the explanation clearly: “According to the authors, the process of indigenous rural exodus is recent and undergone by individuals which, in their place 323 of origin, lived in precarious socio-sanitary conditions.”

Answer: he sentence has been improved.

The case of Venezuela is consistent with the rest of the studies. Why is it highlighted here?

Answer: It was highlighted that Chagas disease prevalence was higher in the urban area due to indigenous people from rural areas who lived there.

 

L325-333. Authors should include a briefer and more global explanation, without describing the specific cases in such detail. The reviews do not have to discuss all the studies, but rather build a synthetic and globalizing knowledge. Only highlight specific issues when essential.

 “The studies of this universe which consider as current residence location, the geographical location and areas vulnerabilities, observed: among 18 rural communities in the state of Piauí, Brazil, significant difference (p<0.001) due to house improvements resulting from intervention programs ([28]; between two Brazilian municipalities, significant difference (p<0.001) justified in reports of coexistence with triatomines in the household ([65]; and between state regions, observing that the geographical and climatologic characteristics of the western region of Sucre, in Venezuela, with coffee tree regions and big climate variation, made the chance of T. cruzi infection 7,4 times greater for the local population in relation to the other regions (p<0.05; OR=7.4) [64].”

Answer: We decided to keep the information; however, we reduced the length of the sentences. Additionally, we included new analyses with the number of cases with significant values and a forest plot.

 

L339-358. Again, authors should build the concept without including specific details. Be careful! with the concept of “unskilled”, this type of concept makes sense in cities, in rural areas, I would ask why extracting açai or being a hunter is a non-qualified job? I am a scientist and I am not qualified to hunt. Perhaps it is important to talk about “formalized work”

Answer: Understood.

 

L359. Be careful!. FORMAL EDUCATION. Rural education especially should be differentiated in planned education by the states (formal) and informal education, more practical, enhanced by families and based on domestic (and rural) activity. If the authors even intend to partially define the concept, they must give a more global, and not just urban, definition of education.

Formal education is probably related to rurality and/or location of residence? It was already explained in reverse. That is because there are interdependent factors that at some point in the study I think should be explained and addressed.

Answer: Here we addressed the level of education that individuals in the community had.

 

 

L368-379; L389-405; L416-432; L441-442; L254-261; L477-531, L550-555; L569-576; L585-603; L605-611 AND SO ON… The same with concrete studies, draw global conclusions, place only the essentially different and important cases; and finally, if necessary, build a Suppl Table displaying these summarized details

Answer: We included forest plot, and we believe that keeping this information helps to visualize the context better.

 

Changes subtitles:

• ACCUMULATION OF WOOD/FIREWOOD IN THE PERIDOMICILE included within PERIDOMICILIARY STRUCTURES BUILDING MATERIAL

Answer: Due to firewood being a material used as a source of energy and heating in homes, or even in ovens for food preparation, the materials of peridomestic structures being used in the construction of animal husbandry spaces, reservoirs, among others, were not discussed together.

 

• PRESENCE OF INFECTED OR NON-INFECTED TRIATOMINES IN THE HOUSEHOLDS = TRIATOMINES IN THE HOUSEHOLDS

Answer: we agreed and changed

 

• PRESENCE OF DOMESTIC ANIMALS IN THE HOUSEHOLDS, INFECTED OR NOT = DOMESTIC ANIMALS IN THE HOUSEHOLDS

Answer: we agreed and changed

 

• PRESENCE OF SINANTROPIC AND/OR WILD ANIMALS IN THE HOUSEHOLDS, INFECTED OR NOT = SINANTROPIC AND/OR WILD ANIMALS IN THE HOUSEHOLDS

Answer: we agreed and changed

 

• PRESENCE OF HUMAN HOST WITH CD = HUMANS WITH CHAGAS DISEASE

Answer: we agreed and changed

• DENSIFICATION OF PEOPLE IN THE INTRADOMICILE = INTRADOMICILIAR HUMAN DENSITY

Answer: we agreed and changed

 

Final Considerations

I would begin this section with the presentation of “collinearity” or interdependence of a large part (or almost all) of the sociocultural and economic factors.

Answer: We believe we have met the requests/recommendations.

 

Conclusions

I think the authors should construct more synthetic conclusions, reduce their number, and do not repeat concepts from different sections. The most global conclusion is the last one. Finally, I think it is important to contextualize the value of the results within next steps in improving the disease, and/or include further studies needed.

Answer: We believe we have met the requests/recommendations. 

 

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

I'm pleased to see that most of the substantive changes requested in the previous rounds have now been adequately addressed. With just a few minor remaining issues, the manuscript appears ready for publication:

1. The duplicated word in the summary at line 26 that was requested to be corrected in the first review has not been addressed.
2. T. cruzi is not italicized on lines 42 and 44.
3. Figure captions are missing, preventing the reader from fully understanding what is depicted.

 

After correcting the minor changes mentioned, I consider that the manuscript will be ready for publication.

 

Beyond correcting those last outstanding items, the manuscript appears to be in good shape. With one final revision to attend to those minor remaining points, I believe the article will then be ready for publication.

Author Response

Dear Review

We thank the reviewer for the corrections and suggestions for improvements in our article. We hope we have addressed them all!

We are available for any further clarifications.

 

Comments and Suggestions for Authors

I'm pleased to see that most of the substantive changes requested in the previous rounds have now been adequately addressed. With just a few minor remaining issues, the manuscript appears ready for publication:

The duplicated word in the summary at line 26 that was requested to be corrected in the first review has not been addressed.

Answer: Sorry for the oversight. It has been corrected now

T. cruzi is not italicized on lines 42 and 44.

Answer: corrected

Figure captions are missing, preventing the reader from fully understanding what is depicted.

Answer: Were included

After correcting the minor changes mentioned, I consider that the manuscript will be ready for publication.

Beyond correcting those last outstanding items, the manuscript appears to be in good shape. With one final revision to attend to those minor remaining points, I believe the article will then be ready for publication.

Answer: We appreciate your contribution to our article

Reviewer 2 Report

Comments and Suggestions for Authors

Predictor variables in the dissemination of the Chagas Disease  in rural areas

Review 2

 

This is my second review of the work. This study presents very interesting information, and should be published. I think the authors have improved some points of the manuscript. I still think the paper is excessively long. Contrary to what was suggested in my first review trying to get a synthesis exercise, in parallel authors carried out an extension of information. In the end the study has not diminished and has not been synthesized. We should write without being repetitive and excessively discursive…. In my opinion, the article is too long, and contrary to the intention of improving the communication channel, the excess of information does not improve communication. For me it has been very easy to tune out the text. My recommendation is that a strong reduction of the text be made, as I commented in my previous review, by 20-30%. I leave this consideration (and others) to the associate editor.

In parallel, and although I am not a native English speaker, an improvement in your writing is necessary.

 

Abstract

L. 20: “The predictor variables yielded significant results (p-value < 0.05) in 59.5% of the 20 cases (195/328), with a median of 66.7%.” This sentence needs further explanation so that readers of the summary understand the meaning.

L. 26: “living in in environments where inhabitability is inadequate”

 

Introduction:

L. 88: “In the US, the autochthonous transmission form is considered rare, even with the awareness of the existence of 10 triatomine specimens in the country which are able to host the T. cruzi. There is also the possibility of encountering these vectors in the wild environment, as well as the risk of infection through blood transfusion and oral transmission.”

It is a repetition, the possibility of finding the vectors is discussed twice. Re-build both sentences.

L- 107. Delete “And”

L. 111: “Over a hundred years after the discovery of CD, the World Health…”

L. 111-113: “Over a hundred years after the discovery of CD the World Health Organization [3] 111 estimates an approximate number of 6 to 7 million of people infected by T. cruzi through-112 out the world, due to human migration [12,13,15,34], being observed another geographical 113 dimension for CD.” This is confusing to me... 6-7 million infections due to migrations? This same sentence is placed in the abstract, but without that reference to migrations.

 

M&M

L. 180. In my opinion, phases 1 and 2 should be joined. The proof is that the number of articles in Fig 2 does not vary. Therefore, the same activities could belong to both phases..

L. 248: Delete “The data analysis is the fifth stage of this research. Initially,”

L. 255 “Dependent predictor variables included epidemiological”

L. 256: “Once the variables were identified, they were analyzed using a Word”, “The variables identified were analyzed using a word…”

L. 260: What is the difference between social and cultural factors?

 

Results and Discusion

Although I am not a native English speaker, it is necessary to improve on this topic, for example, being clearer and simpler when writing. …. L. 282 “We have identified 876 peer-review articles published between 1953 and in 2023, of which 85 articles have been selected for analysis and discussion (Figure 2).” There are some other examples.

 

L. 297. “The analyzed works have been developed 2.4% in Spain, with Latino-American 297 immigrants, and the others countries: Brazil (24.7%), Argentina (22.4%), Mexico (16.5%), 298 Venezuela (12.9%), Colombia (5.9%), Peru (3.5%), Chile (2.5%), Ecuador (2.5%), Bolivia,, 299 Guatemala, Nicaragua, Panamá, Paraguay and Uruguay (3.5% - 1.2%) (Graphic 1)” Order the countries based on decreasing percentages.

L. 307: “Among the studies, 64.7% have been developed also in rural areas.” Delete “also”

L. 312-318. Too long sentence.

L. 318: Try not to begin sentences using “And…”

It is difficult for reviewers to have to make corrections only using the track change systems, but it seems to me that the writing needs to be improved to be able to better understand the concepts. Throughout the discussion, the confusion of the track-change and complicated wording are added, which complicate the understanding of the section.

Change “dissemination” per “spreading”

L. 338: “Graph” I think this is also a Figure

Graph 1. This graph is better than the previous table, but it is important to improve its visibility. My recommendations:

• Authors must clearly explain in the legend the meaning of “Significant results regarding the number of articles for the variable”, “Total number of articles found with significant values” and “Total number of articles found for this variable”

• I think you should choose between “Total number of articles found with significant values” and “Total number of articles found for this variable”

• Finally, place a single column per predictor (Total number of articles found with significant values), and the other number in parentheses (“Significant results regarding the number of articles for the variable”).

 L. 358-360. Excuse my ignorance, but I don't understand how you calculate the median..

L. 406-416. This explanation should be within the legend of the Fig 5

Fg 5. I suggest ordering in decreasing p-value to visualize most important variables. What is the meaning of the number into brackets?

Throughout the Results and Discussion section, there are many paragraphs similar to: “Among the 11 articles with significant values for human with CD, 45.5% showed p > 0.05 or reported, without demonstrating values, that this variable does 864 not significantly influence the number of seropositive cases of CD. Of these articles, only four provided the value, ranging from 0.08 to 0.96. The majority, 54.5%, had p < 0.05. The two articles that presented the OR value found an increase from 1.75 to 4.8 times in the odds of finding an individual with CD due to human with CD”. My recommendation is that authors should think of a more graphical way to include this information. The study is very interesting, but the excess of information without significant information do not help in reading it.

Fig 6. Explanation L-1045-1049 should be within the legend.

Although new Figures have added help understanding, seven Figures are excessive. I recommend eliminating 2 of the figures (probably joining Figs 5,6,7).

 

Conclusion

I don't know if conclusions by points (highlights) are appropriate for the journal. I think it is better to reduce the conclusions and present them in a more synthetic way.

Author Response

Dear Review

We thank the reviewer for the corrections and suggestions for improvements in our article. We hope we have addressed them all!

We are available for any further clarifications.The responses are attached in the PDF.

Author Response File: Author Response.pdf

Round 3

Reviewer 2 Report

Comments and Suggestions for Authors

I believe that the authors have made the required corrections so that I consider that the article can be accepted for publication. Congratulations

Author Response

Thank you for the comments and corrections. We have made the corrections as requested and highlighted them in yellow in the text.

Author Response File: Author Response.docx