We analyzed the patterns of transmission in the 2022 mpox epidemic as it unfolded in the European population of MSM (men who have sex with men). We developed an agent-based model that simulates sexual pair formation, incorporating both brief and longer-term sexual relationships. The model implements survey data on the sexual behavior of MSM and accounts for the highly heterogeneous nature of the sexual contact network within this community. When simulating the mpox epidemic, the model reproduces the reported numbers of sexual partners of mpox-infected patients. We find that natural herd immunity had little impact on ending the European outbreak. Instead, we suggest that the marked decrease in serial interval observed across the epidemic reflects a dramatic increase in self-isolating behavior amongst infected and that this is sufficient to explain the early control of the epidemic. Our work highlights the critical interplay between relationship dynamics and adaptive behaviors in shaping mpox epidemic patterns and achieving control in 2022. Now that the virus is endemic, the European MSM population remains protected by a combined effect of increased awareness and immunity, both natural and vaccine-induced.

Significance Statement The waning of smallpox immunity since its elimination around 1980 leaves an immunological opening to emerging poxviruses. We have witnessed two major mpox outbreaks – clade IIb in 2022 and the ongoing clade Ib in Central Africa – both concentrated in a subpopulation with high-risk sexual behavior. Clade IIb is now endemic and recently surged among Australian MSM. Despite parallels with HIV, particularly its disproportionate burden on MSM, the short infection cycle and subsequent lifelong immunity of mpox imply distinct transmission dynamics. These novel outbreaks demand new modeling approaches and a deeper grasp of herd immunity in highly heterogeneous sexual networks.

The authors have declared no competing interest.

This study was funded by the Danish National Research Foundation (grant no. DNRF170)

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

IRB of Statens Serum Institut gave ethical approval (approval no. 24-06792)

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U.H., K.S. and L.S. designed research; U.H. and K.S. performed research; U.H. and K.S. analyzed data; and U.H., L.S. and K.S. wrote the paper. M.F. provided the Project SEXUS data. All authors critically revised the manuscript.

The authors declare no competing interest.

The survey data used in this study are not publicly available due to confidentiality agreements and participant privacy protections. Simulated data supporting the findings of this study are available upon request. All code used for data processing and analysis will be made publicly available on GitHub prior to publication.