Background The 2022 outbreak of mpox subclade IIb in the Netherlands affected primarily men who have sex with men (MSM). Despite the sharp decline in cases, there are concerns about future mpox outbreaks. We investigated the impact of mpox introductions, accounting for vaccination, behavioural changes, and introductions of subclades with different characteristics. Methods We developed a compartmental model for mpox among MSM. We accounted for three risk levels for mpox, based on sexual activity, and allowed individuals to change risk level. We examined several scenarios with mpox introductions. Results In January 2024, 54% of MSM at high risk for mpox had immunity; this declined to 39% a year later, due to changes in risk levels. Mpox introductions in May 2025 resulted in small outbreaks, but the numbers of cases were 34% or 48% lower with vaccination carried out in August-October 2024 or February-April 2025, respectively, compared to the situation without vaccination in 2024-2025. With earlier initiation or greater magnitude of behavioural adaptations, the number of mpox cases was 17-51% smaller. Introduction of a subclade with 10% higher transmission probability than subclade IIb resulted in 77% more cases. Conclusions Due to changing levels of mpox risk, the fraction immune in the high-risk group will decline, leading to a greater possibilities for future mpox outbreaks. The number of cases can be reduced with preventive vaccination and behavioural adaptations. Recurring vaccination campaigns should prioritise individuals most at risk, ensuring those entering high-risk groups are reached. Campaigns promoting timely behavioural changes remain crucial.

The authors have declared no competing interest.

This study did not receive any funding

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

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

The study used ONLY simulated data or openly available human data: Data with the numbers of daily mpox cases in the Netherlands are freely available on the website of the National Institute of Public Health and Environment of the Netherlands: https://www.rivm.nl/en/mpox/current-information-about-mpox. Data from the PrEP pilot are third-party data from the Dutch national registration of Sexual Health Centre consultations (SOAP); they can be obtained via request to soap@rivm.nl.

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.

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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).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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Data with the numbers of daily mpox cases in the Netherlands are freely available on the website of the National Institute of Public Health and Environment of the Netherlands: https://www.rivm.nl/en/mpox/current-information-about-mpox. Data from the PrEP pilot are third-party data from the Dutch national registration of Sexual Health Centre consultations (SOAP). Pseudonymized individual participant data can be obtained upon reasonable request to the authors or to soap@rivm.nl. All data produced in the present study are available upon reasonable request to the authors.

https://www.rivm.nl/en/mpox/current-information-about-mpox