Oropouche Virus Outbreaks in Northeast Brazil Between 2024-25 are Characterized by Sustained Transmission and Spread to Newly Affected Areas

Oropouche virus (OROV) is a reemerging arbovirus associated with recurrent outbreaks of febrile illness, usually confined to the Amazon biome in South America. However, OROV has recently undergone an extensive expansion in Brazil, establishing local transmission in non-endemic regions, such as Northeast (NE) Brazil. The dynamics of OROV spread and a detailed analysis of sustained transmission chains and features that allow the virus to be maintained in this region are still scarce. Here, we conducted an integrated epidemiological, spatial, and molecular analysis to investigate OROV spread in Northeast (NE) Brazil from March 2024 to April 2025. Confirmed cases were analyzed in relation to ecological risk factors and geographical clustering. Additionally, we generated 65 new OROV genome sequences from the Northeast states of Pernambuco, Paraíba, and Sergipe, and inferred the spatiotemporal dynamics of the virus in the region. A total of 2,806 confirmed cases were reported in Northeast Brazil during the study period, affecting 170 municipalities across eight out of nine NE states, in highly heterogeneous incidence patterns. A notable ecological shift was observed, with OROV transmission moving from Atlantic Forest areas in 2024 to humid zones of Caatinga biome in 2025. Phylogenetic reconstruction revealed multiple independent viral introductions in Northeast in 2024, two of them into Pernambuco. The first, derived from the central region of Amazonas, became the main driver of local transmission and subsequently spread to Paraíba and Sergipe, causing outbreaks. The second, from Rio de Janeiro, remained restricted within Pernambuco. Most cases in Sergipe and Pernambuco were restricted to 2024, while in Paraiba, most cases were recorded in 2025 following a single introduction from Pernambuco. These findings indicate a spatiotemporal displacement of the OROV outbreak in these neighboring states. While several municipalities reported high OROV incidence, Jaqueira (Pernambuco) emerged as a key hub for regional viral spread, with human mobility likely playing a key role in the interstate OROV spread. Despite a shared viral origin, each state experienced a distinct epidemic dynamic, due to different ecoclimatic conditions, short-lived and fast locally spreading outbreaks.