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Transmission dynamics of Oropouche virus in Latin America and the Caribbean. Oropouche virus (OROV) is an arbovirus endemic to the Amazon region since the 1950s that re-emerged in late 2023, causing a major epidemic across Central and South America. Here we investigated the transmission dynamics of the 2023-2024 epidemic in Manaus City (Amazonas state, Brazil), a major metropolitan hub in the Amazon, and estimated OROV infections across Latin America and the Caribbean. OROV re-emergence in Manaus resulted in an increase of IgG seroprevalence from 11.4% in November 2023 to 25.7% in November 2024. The neutralizing capacity of OROV-specific IgG antibodies from individuals collected before and after the re-emergence demonstrated a median plaque reduction neutralization test 50% titer of 640 against both the historical and contemporary OROV isolates. A historical reconstruction of OROV circulation in Manaus indicated a continuous low-level transmission with two major outbreaks of comparable seasonality and magnitude in 1980-1981 and 2023-2024. We estimate approximately 336,000 OROV infections in the Amazon region under a scenario of continuous endemic transmission without major outbreaks and over 9.4 million OROV infections during major outbreaks from 1960 to 2025. Collectively, our findings provide a comprehensive assessment of OROV transmission in Manaus and contribute to a better understanding of the OROV burden.