Santiago Acero-VelasquezSantiago Bautista-LagunaRoger E. Rodríguez-SerranoMarco Arturo RincónSarah Catalina PérezJuan Carlos Santos-BarbosaMaria Fernanda Villalobos-RodriguezJohn Mario González-Escobar2026-03-222026-03-22202610.22541/au.177078250.08749953/v1https://doi.org/10.22541/au.177078250.08749953/v1https://andeanlibrary.org/handle/123456789/79647The global re-emergence of mpox virus (MPXV) during 2022–2024 marked a major epidemiologic shift characterized by sustained human-to-human transmission, rapid geographic spread, and heterogeneous surveillance approaches and testing strategies, resulting in widely variable prevalence estimates across settings. This systematic review aimed to synthesize evidence on MPXV prevalence in adult populations during the 2022–2024 outbreak with particular attention to how population selection, symptom status, and diagnostic approaches shape reported epidemiologic patterns. A PRISMA 2020–compliant search of PubMed, Scopus, and major preprint servers identified studies reporting laboratory-confirmed MPXV infection or prevalence in adults; due to substantial heterogeneity in populations, symptom criteria, and diagnostic methods, analyses were descriptive. Twenty-eight studies including 92,971 individuals identified 12,011 confirmed cases, yielding an overall prevalence of 12.9%, predominantly among young adults (mean age 34.3 years) and symptomatic cohorts. Fever, skin lesions, and lymphadenopathy were most common, with qPCR of skin lesions providing the highest diagnostic yield; clades II and IIb predominated, with incidence peaking in 2022. MPXV epidemiology was shaped by demographic, behavioral, and diagnostic variability, underscoring the need for standardized diagnostics and non-stigmatizing public health interventions.Public healthOutbreakMedicineEnvironmental healthEpidemiologyPublic health surveillanceMEDLINEarticle