Quantifying the population-level impact of expanded antibiotic treatment for cholera outbreak management

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1. 

   PREreview

   Dec 4, 2024

   This Zenodo record is a permanently preserved version of a Structured PREreview. You can view the complete PREreview at https://prereview.org/reviews/14278826.

   Does the introduction explain the objective of the research presented in the preprint? Yes The authors clearly explain the objective of the research and provide proper context on the current cholera burden. The authors begin with explaining the symptoms of cholera and types of clinical manifestations. The next part discusses transmission patterns and treatment regimens. The most common treatment is rehydration, but antibiotics can also be prescribed in extremely severe situations. The authors explain that they are modeling how expanding antibiotic treatment to include moderate to mild …

   This Zenodo record is a permanently preserved version of a Structured PREreview. You can view the complete PREreview at https://prereview.org/reviews/14278826.

   Does the introduction explain the objective of the research presented in the preprint? Yes The authors clearly explain the objective of the research and provide proper context on the current cholera burden. The authors begin with explaining the symptoms of cholera and types of clinical manifestations. The next part discusses transmission patterns and treatment regimens. The most common treatment is rehydration, but antibiotics can also be prescribed in extremely severe situations. The authors explain that they are modeling how expanding antibiotic treatment to include moderate to mild cases can estimate the overall burden of cholera. The model also considered different attack rates seen in the different levels of outbreak scenario by varying the reproductive number, care-seeking behavior, and the proportion of non-severe cases seeing antibiotics.

   Are the methods well-suited for this research? Somewhat appropriate The methods are well suited for the study given the primary concern is whether expanded antibiotic treatment would help curb outbreaks and disease burden. The use of compartmental models and simulations is justified as the more feasible choice when wanting to explore disease burden without requiring large financial backing. The setup of the model and the choice to explore 3 different outbreak scenarios allows the authors to explore the possible effectiveness of antibiotics in different situations and aligns well with their objective. Compartmental modeling and LHS fit the parametric approach and are an appropriate choice. Additional input from a modeling expert to ensure parameters were appropriately chosen would be required to further bolster the rigor and validity. However, the model has some key limitations - some of which are mentioned by the authors and others are not. The authors acknowledge their model fails to characterize many parameters surrounding cholera and their choice to assume certain states such as no prior immunity. While their study captures a wide array of cholera and its impact, leaving out certain factors affects the generalizability of their study, especially to real world situations. To improve: The authors mention they "do not attempt to parameterize care seeking behavior, rather, [they] vary the proportion of non-severely symptomatic infections who seek care between simulations". How does the model then accurately predict care seeking behaviors when some of the model's parameters are not well characterized for cholera? Elaborate on how the model and study account for this limitation. Although the model also does not account for the evolution of resistance, the authors explain they use "the number of antibiotic doses administered as a proxy". Further explain exactly how antibiotic doses serve as a proxy for resistance The model does not include the impact of prior immunity on cholera outbreaks and their management. The paper also does not mention other forms of immunity such as vaccination. The authors should acknowledge their choice to assume no prior immunity as a limitation of their study as this fails to reflect many real life scenarios.

   Are the conclusions supported by the data? Somewhat supported The conclusions are reasonable and not overreaching interpretations of the data. The authors adequately highlighted the limitations of each of their claims. For example, when the authors compare the treatment of non-severely symptomatic infections in reducing cholera burden between low and high Re (effective reproductive number) settings, they acknowledge that their claim only considers expanding antibiotic treatment guidelines, but antibiotic use can also be combined with other outbreak containment interventions in the real-world. Minor Concerns: The conclusions are generally supported by the data and results of the study, but the writing could be improved to clearly reference the relevant data. For example, the authors make several claims throughout the discussion with references to the results of the study, but do not consistently cite specific significant findings from the results. For example, authors state that "the effectiveness of expanding antibiotic treatment criteria improves as the proportion of non-severely symptomatic infections seeking care increases." In addition to this statement, the authors can reference back to the significant results and findings of Figure 2. Overall, the conclusions are not overreaching, but the authors can clearly clarify the assumptions of their claims such as restating that the evolution of antibiotic resistance was not modeled and the number of antibiotic doses administered was used as a proxy for selective pressure.

   Are the data presentations, including visualizations, well-suited to represent the data? Somewhat appropriate and clear We would recommend that the font sizes are enlarged on the axes to make it easier to read and be more in line with best accessibility practices. It would be helpful to highlight the mild-moderate group to help orient the readers to the most important focus of the paper.

   How clearly do the authors discuss, explain, and interpret their findings and potential next steps for the research? Somewhat clearly The authors explain that certain circumstances would benefit from antibiotic treatment, as it reduces transmission and limits the extent of outbreaks for low and intermediate transmission. The discussion emphasizes their results regarding antibiotic use in low and high Re settings, and they note that as Re increases, the benefit of antibiotic use decreases until there is a high-transmission setting. However, the authors could further explain how the threat of antibiotic resistance varies in respect to the different transmission levels. The limitations of the study are effectively addressed in the discussion. The authors then encourage future studies to conduct research that considers the limitations of this study, especially characterizing parameters of the model for cholera and assessing the feasibility of implementing the model.

   Is the preprint likely to advance academic knowledge? Somewhat likely The preprint makes several noteworthy contributions to the role and potential benefit of antibiotics in cholera outbreak management, especially for non-severely symptomatic infections. The authors' use of compartmental models and comprehensive simulations provide valuable insight into the effectiveness difference of treating non-severe symptomatic infections with antibiotics under different transmission outbreak scenarios, varying reproductive number, care-seeking behavior, and proportion of non-severe cases receiving antibiotics. However, the preprint does not provide substantial contributions that advance our understanding of the subject matter as it is confirmatory of prior research that has suggested that "under certain circumstances, expanding antibiotic treatment of cholera cases can provide population-level benefits". Hence, while the preprint makes meaningful contributions under which circumstances expanding antibiotic treatment can provide population-level benefits, it mostly reconfirms our understanding of the subject matter.

   Would it benefit from language editing? No

   Would you recommend this preprint to others? Yes, but it needs to be improved After acknowledging some of the further limitations of the study, it could be helpful in aiding treatment decisions for people who are managing cholera in non-endemic regions. Additionally, those who are interested in understanding patterns of antibiotic treatment expansion/resistance patterns in cholera would find this as an additional validating guidance for treatment expansion in certain regions.

   Is it ready for attention from an editor, publisher or broader audience? Yes, after minor changes We would recommend attention from a modeling expert to ensure validity of the parameters chosen prior to wider dissemination.

   Competing interests

   The authors declare that they have no competing interests.

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2. 

   Version published to 10.1101/2024.11.04.24316579v1 on medRxiv

   Nov 5, 2024