Review 1: "Estimating the Burden of Mpox Among MSM in South Africa"

RR\ID Evidence Scale rating by reviewer:

• Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable, unless the weaknesses are clearly understood and there is other theory and evidence to further support it.

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Review: In this manuscript, the authors estimate the potential number of mpox Clade II cases in South Africa using published estimates and four different scenarios. This manuscript is well-written and provides critical insight into the need for enhanced surveillance to mitigate the disease burden. However, I believe certain aspects could be clarified, and I hope these suggestions enhance the manuscript's impact.

1. I wonder if the case fatality risk (CFR) of mpox Clade II could be time-varying, particularly following the allocation of the JYNNEOS vaccine. This might be particularly relevant if vaccine effectiveness against death is significantly higher than against infection. Was there any vaccine allocation in South Africa targeting the MSM population (or was there any vaccine campaign against smallpox)? If so, could the author provide details on the coverage and its potential impact on CFR? Additionally, further clarification regarding the cited paper, where the authors mentioned the CFR (in the first paragraph of Model Parameterization), would be beneficial for readers who may not be familiar with it.

2. I suggest the authors clarify the source of the 17.8% of CFR presented in Table 1, as the values of 15.1% (for those with CD4+ T cell counts < 200) and 27.1% (for those with CD4+ T cell count < 100) are only mentioned in the Method section. Additionally, I am curious as to why the mean value was used instead of the median. Furthermore, it appears there is a typo in the 95% confidence interval for mpox CFR among PLAHIV (the interval does not include the mean value).

3. Did the author account for the uncertainty inherent in the proportion of cases with advanced HIV (which was estimated as 6.6% using the Thembsia model)? I did not find any mention of this uncertainty in the current manuscript. Additionally, I would suggest that the authors provide the 95% confidence intervals for the borrowed estimates (not just in Table 1).

4. I could not clearly follow which estimates the authors used to calculate the alpha. Does this imply that serological information was utilized to reduce biases in the prevalence of HIV among mpox cases? I also presume the case ascertainment of mpox among individuals with HIV might be significantly higher than other MSM populations, potentially biasing these estimates. Do the authors have any insights or empirical evidence regarding this?

Minor comments:

1. The median and confidence intervals can be included in the Abstract.

2. The term "advanced HIV" can be defined in the Introduction part when it is first mentioned.