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Extensive cryptic circulation sustains mpox among men who have sex with men

Lewnard, J.; Paredes, M. I.; Yechezkel, M.; Davis, G. S.; Hong, V.; Skela, J.; Pandey, U.; Parker, N. T.; Granskog, L. C.; Pomichowski, M. E.; Reyes, I. A. C.; Rodriguez Barraquer, I.; Mueller, N. F.; Tartof, S. Y.

2025-08-13 epidemiology
10.1101/2025.08.09.25333368 medRxiv
Show abstract

Sporadic cases of mpox continue to be notified among men who have sex with men (MSM), with most lacking identifiable transmission links. To resolve underlying dynamics, we tested prospectively for monkeypox virus (MPXV) in rectal swabs from a cohort of MSM in Los Angeles, whom we monitored concurrently for clinical mpox diagnoses during summer, 2024. Here we show that MPXV infections exceeded reported mpox cases by a 33-fold margin (95% confidence interval: 16-68), revealing incidence rates of MPXV infection comparable to Neisseria gonorrhoeae and Chlamydia trachomatis among MSM. Independent estimates derived from MPXV phylogenetic reconstruction and a meta-analysis of surveillance studies corroborated this extensive under-reporting. We estimate that undiagnosed infections must cause at least 31-44% of all transmission to explain observed MPXV phylogenies; under realistic modeling assumptions, this proportion rises to 61-94%. Contrary to current guidance, our findings suggest MPXV is prevalent among MSM, predominantly causes subclinical infection, and is sustained in circulation by cryptic transmission. The feasibility of current mpox elimination targets merits assessment in light of prevalent and extensively under-reported infections.

Published in Nature Communications (predicted rank #1) · training set

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