Review 2: "Estimating the Burden of Mpox Among MSM in South Africa"

RR\ID Evidence Scale rating by reviewer:

• Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.

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Review: The preprint "Estimating the burden of mpox among MSM in South Africa" analyzes potential underreporting of mpox cases among men who have sex with men (MSM) in South Africa. Using a Monte Carlo simulation model, the study estimates that between 290 and 1,600 cases likely exist, considering the higher severity of mpox among individuals with advanced HIV.

Strengths of the Study:

The authors use Monte Carlo simulations to account for uncertainties in key parameters, such as the case fatality ratio (CFR) among PLAHIV. This approach is well-suited for estimating the potential range of undetected cases, providing a rigorous framework for addressing data limitations. Additionally, the study draws on both global and local data, using findings from global research on mpox severity in people with HIV and integrating local HIV prevalence estimates among MSM in South Africa. This dual consideration of global trends and regional context adds credibility to the findings, making them more applicable to local public health planning.

The authors also include sensitivity analyses, which assess how varying definitions of advanced HIV (e.g., CD4+ T-cell count thresholds) affect the estimates. These analyses enhance the study's robustness by exploring different scenarios and providing plausible ranges for the number of mpox cases. The authors’ transparency regarding their assumptions and their acknowledgment of potential biases in the data lend further strength to their approach.

Areas for Consideration:

Despite its strengths, the study has some limitations that merit consideration. One key issue is the reliance on global data to estimate mpox severity in people with advanced HIV in the South African context. While using these estimates is reasonable given the limited local data, differences in healthcare access, social determinants, and management of HIV could influence the generalizability of the findings. As a result, the study’s conclusions should be interpreted with caution, particularly regarding the precise estimates of the true case burden.

Another limitation is the focus solely on the MSM population. While this aligns with global transmission patterns of mpox, it may overlook potential spread to other groups, such as heterosexual partners or other communities. This limitation means the study could underestimate the overall burden of mpox in South Africa, particularly if cases in other populations remain undetected. Addressing this limitation in future research would provide a more comprehensive understanding of the outbreak’s dynamics.

Implications for Policy and Public Health:

The study's findings have key implications for public health in South Africa, emphasizing the need for better surveillance, targeted outreach, and increased testing among high-risk groups due to likely underreporting. These recommendations are well-supported by the evidence and are vital for controlling the outbreak. It also highlights the vulnerability of individuals with advanced HIV, guiding resource allocation and care strategies.