Zoonotic Diseases in Sub-Saharan Africa: A Systematic Review and Meta-Analysis

Round 1

Reviewer 1 Report

The study on "Zoonotic diseases in sub-Saharan Africa: A Systematic Review and Meta-analysis" informs us that frequent animal-human interactions in sub-Saharan Africa pose an increased risk of zoonotic disease transmission. The study conducted a systematic review of zoonotic disease studies conducted between 2000 and 2022 in the region. The analysis of 55 eligible articles revealed 82 reports of zoonotic diseases, resulting in 28,934 human cases and 1,182 deaths. The study emphasizes the need for surveillance and response preparedness, identifying high-risk diseases that should be prioritized. It also calls for the strengthening of health systems and the implementation of a One Health approach. Encouraging research during ongoing epidemics is stressed to enhance immediate response strategies and prevent future outbreaks. However, in my opinion following aspects of the manuscript must be addressed before accepting it for the publication.

The abstract does not specify the specific countries or regions within sub-Saharan Africa that were included in the review. SSA is a vast and diverse region with varying healthcare systems, ecological contexts, and disease burdens. Failing to provide this information may limit the generalizability of the findings and hinder the ability to address specific regional variations. The criteria for including studies are not explicitly mentioned in the abstract. It is unclear how the 55 eligible articles were identified and selected for inclusion.

The introduction does not explicitly state the research question or objective of the review article. It is important for a systematic review to clearly define the specific aim or research question that the study seeks to address. Without a clear research question, it may be challenging to assess the relevance and focus of the review. Further, the introduction provides some general information about animal-human interactions and the economic significance of animal husbandry in sub-Saharan Africa. However, it does not sufficiently contextualize the prevalence, impact, or consequences of zoonotic diseases in the region. A more comprehensive overview of the burden of zoonotic diseases in sub-Saharan Africa would provide a stronger foundation for the subsequent analysis.

The search included articles indexed until November 21, 2022. By limiting the search to a specific date range, there is a possibility that more recent studies or emerging data on zoonotic diseases in sub-Saharan Africa may have been missed. This limitation may affect the comprehensiveness and currency of the review's findings. Additionally, the methodology states that the assessment of reports for quality was not stringent to allow inclusion of reports with some information on zoonotic outbreaks. The lack of a rigorous quality assessment may introduce studies with potential bias or low-quality data, which could affect the overall reliability and validity of the review's findings.

The results mention that 1,182 deaths were reported from zoonotic diseases, and the overall pooled CFR was 345.4 per thousand. However, the specific CFRs for individual diseases are only provided for anthrax (55.0 per thousand) and Marburg (802.1 per thousand). The omission of CFRs for other diseases limits the completeness of the analysis and makes it difficult to compare the severity of different zoonotic diseases. The results state that only 37.8% of the included studies were conducted during ongoing outbreaks. This indicates a potential reporting bias, as studies conducted during outbreaks may provide different insights and data compared to studies conducted in non-outbreak settings. The reliance on non-outbreak studies may introduce bias in the overall analysis and limit the generalizability of the findings.

The discussion states that the conclusions of the review cannot be directly applied to real-life active epidemic settings for different zoonotic diseases due to the limited inclusion of studies conducted during ongoing outbreaks. However, the discussion does not elaborate on the potential implications or consequences of this limitation. Providing a deeper analysis of the impact of the limited inclusion of ongoing outbreak studies would enhance the understanding of the review's findings. The discussion does not provide specific recommendations or suggestions for future research or actions. It briefly mentions the need for surveillance systems, capacity building, and global collaboration but does not provide concrete steps or strategies to address the identified limitations and knowledge gaps. A more robust discussion of future directions would enhance the practical relevance and applicability of the review's findings.

Minor editing of English language required

Author Response

Reviewer #1

Comment 1: The abstract does not specify the specific countries or regions within sub-Saharan Africa that were included in the review. SSA is a vast and diverse region with varying healthcare systems, ecological contexts, and disease burdens. Failing to provide this information may limit the generalizability of the findings and hinder the ability to address specific regional variations. The criteria for including studies are not explicitly mentioned in the abstract. It is unclear how the 55 eligible articles were identified and selected for inclusion.

Response 1: While the full text provides all details about the included study sites, we were concerned about the word limit of the abstract and initially decided to omit the countries. We agree with the reviewer that SSA is a vast area, and we may need to be a little more specific about the areas of interest. As per the reviewer’s request, and to keep within the journal’s abstract’s word count, we now propose to list the parts of SSA that were involved in this systematic review (West, Central, East and Southern Africa). We have also expounded on the eligibility criteria in the abstract. The amended text in the abstract reads as follows: “Quantitative reports including case reports/series which hailed from countries spanning West, Central, East, and Southern SSA and which provided empirical data on the occurrence of zoonotic diseases in humans with documented evidence of animal origin were eligible for inclusion.”

Comment 2: The introduction does not explicitly state the research question or objective of the review article. It is important for a systematic review to clearly define the specific aim or research question that the study seeks to address. Without a clear research question, it may be challenging to assess the relevance and focus of the review. Further, the introduction provides some general information about animal-human interactions and the economic significance of animal husbandry in sub-Saharan Africa. However, it does not sufficiently contextualize the prevalence, impact, or consequences of zoonotic diseases in the region. A more comprehensive overview of the burden of zoonotic diseases in sub-Saharan Africa would provide a stronger foundation for the subsequent analysis.

Response 2: We have now added more information in the introduction to highlight the burden of zoonotic diseases in this part of the globe. However, since these diseases often occur in outbreaks, it is hard to discuss their prevalence. We have also clearly stated the objective of the study in the introduction. The following text was added: “From 2012 to 2022, the rate of zoonotic disease outbreak in SSA increased by 63% compared to the preceding decade (2001–2011). From 2001 to 2022, 33% of public health emergencies in this part of the globe were zoonotic disease outbreaks [14]. The death of people and animals (which contribute immensely to the economy), morbidity, and travel restrictions that occur as direct and indirect consequences of zoonotic disease outbreaks impose a heavy burden on the economies and health systems of the nations concerned.”

Comment 3: The results mention that 1,182 deaths were reported from zoonotic diseases, and the overall pooled CFR was 345.4 per thousand. However, the specific CFRs for individual diseases are only provided for anthrax (55.0 per thousand) and Marburg (802.1 per thousand). The omission of CFRs for other diseases limits the completeness of the analysis and makes it difficult to compare the severity of different zoonotic diseases. The results state that only 37.8% of the included studies were conducted during ongoing outbreaks. This indicates a potential reporting bias, as studies conducted during outbreaks may provide different insights and data compared to studies conducted in non-outbreak settings. The reliance on non-outbreak studies may introduce bias in the overall analysis and limit the generalizability of the findings.

Response 3: Figure 4 reports the CFR for each disease, therefore we only mentioned the extreme numbers in the text. We apologize if Fig 4 was not visible in the submitted version, we have now ensured that all figures and tables have uploaded properly in the manuscript.

Comment 4: The discussion states that the conclusions of the review cannot be directly applied to real-life active epidemic settings for different zoonotic diseases due to the limited inclusion of studies conducted during ongoing outbreaks. However, the discussion does not elaborate on the potential implications or consequences of this limitation. Providing a deeper analysis of the impact of the limited inclusion of ongoing outbreak studies would enhance the understanding of the review's findings. The discussion does not provide specific recommendations or suggestions for future research or actions. It briefly mentions the need for surveillance systems, capacity building, and global collaboration but does not provide concrete steps or strategies to address the identified limitations and knowledge gaps. A more robust discussion of future directions would enhance the practical relevance and applicability of the review's findings.

Response 4: We have now re-written the paragraph on study limitations to highlight the implications of using data from outbreaks versus non-outbreak contexts. In the results, we now report an additional analysis for attack rate and CFR, stratified by outbreak setting. In the discussion, the edited text reads as follows: “First, the studies we included differed widely in terms of methodology and population. This high heterogeneity made it difficult to draw certain solid conclusions. Therefore, more precise information can be obtained by conducting site-specific studies for the identified zoonotic diseases using a uniform study design to ease comparisons. Second, only 37.8% of the studies we included were conducted during ongoing outbreaks which implies that our overall conclusions can hardly be applied directly to real-life active epidemics settings for the different zoonotic diseases. Nevertheless, stratification of the extracted data found that attack/fatality rates were generally lower during outbreaks since more people are routinely screened as part of the epidemic response, and this inflates the denominator compared to non-outbreak settings whereby only suspected cases are tested. Third, the risk of bias was also high for many of the included studies since they were mostly cross-sectional investigations. Therefore, we recommend that more cohort studies (including continuous surveillance) to corroborate our findings and explore other relevant aspects in the epidemiology of zoonotic diseases.”

Reviewer 2 Report

There are few points need to be mentioned in the study;

·         Overall, 55 articles and 82 reports were reviewed and neither of the included studies mentioned the mesoendemic diseases that can be a potential threat in SSA region nor they highlighted the antimicrobial resistance that can be an important factor in zoonotic diseases.

·         Although, overall discussion chapter is well comprehended, but control strategies for the zoonotic spillover of the zoonotic diseases according to quadripartite (WHO, FAO, WOAH, and UNEP) set standards can be suggested in the discussion.

·       There are few typo mistakes of spacing. About figure 4 (Pooled case fatality rates for the included zoonotic diseases) and figure 2 (Number of zoonotic diseases reports per country in sub-Saharan Africa) is mentioned in the text but are not present in the article nor in appendices.

Author Response

Reviewer #2

Comment 1: Overall, 55 articles and 82 reports were reviewed and neither of the included studies mentioned the mesoendemic diseases that can be a potential threat in SSA region nor they highlighted the antimicrobial resistance that can be an important factor in zoonotic diseases.

Response 1: The aim of the review was not to identify mesoendemic diseases, but all zoonotic diseases that have previously been reported in SSA since we should be prepared for possible resurgence of any of them, including newer diseases. Concerning antimicrobial resistance, we agree with the reviewer that it is certainly a relevant factor to consider in zoonotic diseases. We have now added this in the discussion: “Another looming threat for zoonotic outbreaks is the misuse of antimicrobials in animals which fosters the development of resistances and eventually leading to human infections via a food web or otherwise [88]. Here again, a one health approach would be necessary to control antimicrobial use in animals and the environment at large.”

Comment 2: Although, overall discussion chapter is well comprehended, but control strategies for the zoonotic spillover of the zoonotic diseases according to quadripartite (WHO, FAO, WOAH, and UNEP) set standards can be suggested in the discussion.

Response 2: We agree with the reviewer, and now include the following text in the discussion: “It is in this light that a quadripartite agreement was signed between the Food and Agriculture Organization (FAO), the World Organization for Animal Health, the UN Environment Program (UNEP) and the World Health Organization (WHO) in 2022 to strengthen cooperation to sustainably balance and optimize the health of humans, animals, plants, and the environment by leveraging on One Health approaches [93].

Comment 3: There are few typo mistakes of spacing. About figure 4 (Pooled case fatality rates for the included zoonotic diseases) and figure 2 (Number of zoonotic diseases reports per country in sub-Saharan Africa) is mentioned in the text but are not present in the article nor in appendices.

Response 3: We apologize if the figures could not be found in the previous version of the manuscript. We have now insured that they are properly uploaded in the current revised version.

Reviewer 3 Report

The authors have provided an interesting account of references relevant to zoonotic diseases in Africa.

 

Major issues.

The objectives of the study must be clearly described.

The Prisma guidelines must be presented in brief.

Figure 2 is missing.

 

 

Minor issues.

Most of the Introduction includes well-known information (some of which is not fully accurate as well), hence I suggest to delete altogether.

Table 1: please move to Appendix.

Figure 3: please move to supplementary material.

Please, do not repeat results in the Discussion.

Discussion can be divided into 2 or 3 sub-sections.

 

Overall. There is potential for publication, but improvement as indicated must be performed.

Author Response

Reviewer #3

Comment 1: The objectives of the study must be clearly described.

Response 1: This has now been stated in the introduction: “In this paper, we aimed to map some common zoonotic diseases which have been reported in SSA during the current century and identify their reservoirs and associated mortality and/or morbidity rates.”

Comment 2: The Prisma guidelines must be presented in brief.

Response 2: We have now added the following paragraph to detail the PRISMA guidelines: “We followed the PRISMA 2020 guidelines [15]. These guidelines lay out the internationally approved methods for conducting systematic reviews; the process starts by conducting a systematic search in the target databases using well defined keywords to retrieve abstracts of potentially eligible publications. After screening of abstracts based on eligibility criteria, the remaining reports must be sought and the full papers read in detail to determine whether they comply with the inclusion criteria for the review. At each stage, the reasons for non-inclusion should be noted until the eligible reports are identified for data extraction and analysis.”

Comment 3: Figure 2 is missing.

Response 3: We apologize, it has been provided in the revised version of the manuscript.

Minor issues

Comment 4: Most of the Introduction includes well-known information (some of which is not fully accurate as well), hence I suggest to delete altogether.

Response 4: We have now reviewed the introduction. We think it is important to maintain it in the text for the naïve reader to get informed about the concepts of zoonotic diseases before diving into our methods and results.

Comment 5: Table 1: Please move to Appendix.

Response 5: We think that this table is very informative and we propose to keep it in the text. Additional information have indeed been sent to the Supplementary Appendix.

Comment 6: Figure 3: please move to supplementary material.

Response 6: We think that this figure is very informative and we propose to keep it in the text.

Comment 7: Please, do not repeat results in the Discussion.

Response 7: We agree that the results should not be reported in the discussion. However, it is worth briefly mentioning a given finding before elaborating on it in the discussion. This is the approach we used.

Comment 8: Discussion can be divided into 2 or 3 sub-sections.

Response 8: We have presented the discussion in separate paragraph to address different issues.

Round 2

Reviewer 1 Report

I am pleased to know that the authors have addressed the comment and have substantially improved the manuscript. It is my pleasure to recommend the manuscript for publication in its present form.

Author Response

We thank the reviewer for insightful comments which allowed us to improve the manuscript.

Reviewer 3 Report

The authors have improved the manuscript significantly.
Before acceptance, I suggest again that possibly figures 3 and 4 could be transferred to supplementary material, as they are too detailed and really may not catch the attention of future readers.
After that, the manuscript will be ready for acceptance.

Author Response

We thank the reviewer for the comments given thus far, which have allowed us to greatly improve the manuscript. Regarding Figures 3 and 4, we strongly feel they should be kept in the main text because this paper presents results of a meta-analysis (as indicated in the manuscript title). A distinct feature of meta-analytic papers is the presentation of forest plots (Figs 3 and 4) which synthesize the extracted evidence. So we think it would be useful to the readers to have these diagrams in the paper. Thank you.