Rapid Viral Expansion Beyond the Amazon Basin: Increased Epidemic Activity of Oropouche Virus Across the Americas

Summary: Oropouche virus (OROV), initially detected in Trinidad and Tobago in 1955, has been historically confined to the Amazon Basin. However, since late 2022, OROV has been reported in northern Brazil as well as urban centers in Bolivia, Colombia, Cuba, and Peru. Herein, we describe the doubling of publicly available full genomes by generating 133 new entries. We show how the virus evolved via genome component reassortment and how it rapidly spread across multiple states in Brazil, causing the largest outbreak ever recorded outside the Amazon basin including the first ever detected deaths. This work highlights the need for heightened epidemiological and genomic surveillance and the implementation of adequate measures in order to mitigate transmission and the impacts on the population. Background: Oropouche virus was first identified in 1955 in Trinidad and Tobago and later found in Brazil in 1960. Historically, it has been reported to have caused around 30 outbreaks, mostly within the Amazon Basin, where it circulates among forest animals, but also in urban areas where it is known to be transmitted by the midge Culicoides paraensis. Recently, Brazil has seen a surge in cases, with more than 7000 reported by mid-2024 alone. Methods: In a collaboration with Central Public Health Laboratories across Brazilian regions, we integrated epidemiological metadata with genomic analyses of recently sampled cases. This initiative resulted in the generation of 133 whole genome sequences from the three genomic segments (L, M, and S) of the virus, including the first genomes obtained from regions outside the Amazon and from the first ever recorded fatal cases. Findings: All of the 2024 genomes form a monophyletic group in the phylogenetic tree with sequences from the Amazon Basin sampled since 2022. Our analyses revealed a rapid north-to-south viral movement from the Amazon Basin into historically non-endemic regions. We identified 21 reassortment events, although it remains unclear if genomic evolution of the virus enabled the virus to adapt to local ecological conditions and evolve new phenotypes of public health importance. Interpretation: Both the recent rapid spatial expansion and the first reported fatalities associated with Oropouche (and other outcomes under investigation) underscore the importance of enhancing surveillance for this evolving pathogen across the Region. Without any obvious changes in the human population over the past 2 years, it is possible that viral adaptation, deforestation and recent climate change, either alone or in combination, have propelled Oropouche virus beyond the Amazon Basin.