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By performing phylogeographic analysis of MPXV genomes sampled from 757 individuals in NYC between April 2022 and April 2023, and 3,287 MPXV genomes sampled around the world, we identify over 200 introductions of MPXV into NYC with at least 84 leading to onward transmission. These infections primarily occurred among men who have sex with men, transgender women and nonbinary individuals. Through a comparative analysis with HIV in NYC, we find that both MPXV and HIV genomic cluster sizes are best fit by scale-free distributions, and that people in MPXV clusters are more likely to have previously received an HIV diagnosis and be a member of a recently growing HIV transmission cluster. We model MPXV transmission through sexual contact networks and show that highly connected individuals would be disproportionately infected at the start of an epidemic, which would likely result in the exhaustion of the most densely connected parts of the network, and, therefore, explain the rapid expansion and decline of the NYC outbreak. By coupling the genomic epidemiology of MPXV and HIV with epidemic modeling, we demonstrate that the transmission dynamics of MPXV in NYC can be understood by general principles of sexually transmitted pathogens.<\/jats:p>","DOI":"10.1038\/s41591-025-03526-9","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T21:27:01Z","timestamp":1742938021000},"page":"1464-1473","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Transmission dynamics of the 2022 mpox epidemic in New York City"],"prefix":"10.1038","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0977-2886","authenticated-orcid":false,"given":"Jonathan E.","family":"Pekar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8855-0925","authenticated-orcid":false,"given":"Jade C.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yucai","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faten","family":"Taki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A.","family":"Forgione","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helly","family":"Amin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3887-4510","authenticated-orcid":false,"given":"Tyler","family":"Clabby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia V.","family":"Torian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah L.","family":"Braunstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preeti","family":"Pathela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enoma","family":"Omoregie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8882-2946","authenticated-orcid":false,"given":"Scott","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9818-479X","authenticated-orcid":false,"given":"Marc A.","family":"Suchard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetyana I.","family":"Vasylyeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2826-5353","authenticated-orcid":false,"given":"Philippe","family":"Lemey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4882-5856","authenticated-orcid":false,"given":"Joel O.","family":"Wertheim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,25]]},"reference":[{"key":"3526_CR1","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1126\/science.adg8116","volume":"382","author":"\u00c1 O\u2019Toole","year":"2023","unstructured":"O\u2019Toole, \u00c1. et al. 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