Dynamic landscape of mpox importation risks driven by heavy-tailed sexual contact networks among men who have sex with men in 2022: a mathematical modeling study

Background The 2022 global mpox outbreak spread rapidly, primarily among men who have sex with men in Western countries. The number of countries with new mpox importation events quickly rose in the early phase of the outbreak, but the rate of increase subsequently slowed down, having many countries without any reported cases. Methods We developed a mathematical model of international dissemination of mpox infections that accounts for heterogeneous sexual contact networks, infection-derived immunity in the network, and global mobility of infectious individuals. We used this model to characterize the mpox importation patterns observed in 2022 and to discuss the potential of further international spread. Findings Our analysis showed that the proposed model better explained the observed importation patterns than models not assuming heterogeneity in sexual contacts. Estimated importation hazards decreased from August 2022 in most countries, faster than the decline in the global case counts. We assessed each country’s potential to export mpox cases until the end of an epidemic in the absence of interventions and behavior changes, identifying countries capable of contributing to future international spread if they experience sustained local transmission. Interpretation Our study suggested that the accumulation of immunity among high-risk individuals over highly heterogeneous sexual networks may have contributed to the slowdown in the rate of mpox importations. However, our analysis identified the existence of countries still with the potential to contribute to the global spread of mpox, particularly those with sizable susceptible populations and large international travel volume. This highlights the importance of ensuring equitable access to treatments and resources to prevent the global resurgence of mpox. Evidence before this study Mathematical models incorporating interconnectivity between countries have been used to assess the risk of international disease introductions. These approaches have assumed homogenously mixing local populations and have been successful in capturing the international importation patterns observed in previous global respiratory infection outbreaks such as influenza and COVID-19. However, it remains uncertain whether these models can be extended to the context of mpox, which has been transmitted predominantly through sexual activities among men who have sex with men. Previous studies have underpinned the significant role of infection-derived immunity in highly heterogeneous sexual networks in slowing down its transmission. Such key characteristics of mpox have not yet been incorporated in existing approaches to assessing the risk of international spread, which may lead to misguided public health decision-making. Added value of this study We constructed a mathematical model of international dissemination of mpox infections considering heterogeneous sexual networks and infection-derived immunity, as well as the global mobility of infectious individuals. By applying this model to the observed mpox importation patterns in 2022, we found that incorporating the accumulation of immunity among high-risk individuals better explains the observed slowdown in the rate of mpox importations between countries. Additionally, the model highlighted the presence of countries that still have the potential to contribute to the global spread of mpox, particularly those with large susceptible populations and a high volume of international travel. Implications of all the available evidence Our study adds to the growing evidence on the role of accumulated immunity among high-risk individuals in the slowdown the mpox transmission in the 2022 outbreak, which we found to be also the key to better understanding the global importation patterns. Without incorporating this effect, existing modeling approaches may overestimate the mpox importation risks, especially from countries where high-risk groups have already acquired immunity early in the outbreak. Furthermore, our visualization of large susceptible populations remaining in less affected countries, including low- and middle-income countries, highlights the importance of assessing the onward risk of case importation and ensuring equitable access to treatment and control measures in these at-risk countries. ### Competing Interest Statement FM receives a grant from AdvanSentinel Inc. on the project of wastewater monitoring. ### Funding Statement S-mJ and JL are supported by the Centers for Disease Control and Prevention (CDC) SHEPheRD (200-2016-91781). FM is supported by JSPS Grants-in-Aid KAKENHI (20J00793 and 21KK0107). FM and JW received funding from the European Union's Horizon 2023 research and innovation programme - project ESCAPE (Grant agreement number 101095619). AE is supported by Japan Society for the Promotion of Science (JSPS) Overseas Research Fellowships, JSPS Grants-in-Aid KAKENHI (22K17329), foundation for the Fusion Of Science and Technology, and Japan Science and Technology Agency (JST) Precursory Research for Embryonic Science and Technology (JPMJPR22R3). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The aggregated and case-based data has been available on the WHO website and the estimated MSM population size data has been available on the UNAIDS dashboard and report. The replication codes and all utilized data, except for the international travel volume data which was obtained from UNWTO, are available at: .