Rapid spatial Expansion Beyond the Amazon Basin: Oropouche Virus joins other main arboviruses in epidemic activity across the Americas

SummaryThe Oropouche virus, initially detected in Trinidad and Tobago in 1955, has been historically confined to the Amazon Basin. However, since late 2022, it has been reported elsewhere, from northern Brazil to urban centers in Bolivia, Colombia, Cuba, and Peru. In this report we describe the doubling of publicly available full genomes by generating 133 new entries. We show how the virus evolved via recombination 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 responses in order to avoid Oropouche becoming another widespread arboviral public health threat. BackgroundThe 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, most of which 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 6000 reported by mid-2024 alone. MethodsIn 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. FindingsAll of the 2024 genomes form a monophyletic clade in the phylogenetic tree with sequences from the Amazon Basin sampled since 2022. Our analyses reveal a fast and clear pattern of north-to-south viral movement from the Amazon Basin into historically non-endemic regions. We identified 21 recombinant events, but it remains unclear if such genomic changes mirror potential adaptations and the emergence of new viral phenotypes of public health importance. InterpretationBoth the recent rapid spatial expansion and the first reported fatalities associated with Oropouche underscore the importance of enhancing surveillance at both national and continental levels. Without any obvious changes in the human population over the past 2 years, it remains likely that either alone or in combination, viral adaptation, deforestation and climate change trends in the recent past may have propelled the Oropouche virus beyond the Amazon Basin. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSBefore this study, the Oropouche virus was known to cause periodic outbreaks primarily within the Amazon Basin. Initially identified in Trinidad and Tobago in 1955, the virus had been responsible for approximately 30 outbreaks in Latin America, mostly confined to the Amazon region. The virus typically circulates among forest animals and is transmitted to humans by the bite of the midge Culicoides paraensis. There has been an historical dearth of available genomic data, and so far the spread beyond the Amazon Basin has not been well-documented. Added value of this studyThis study provides a timely and comprehensive analysis of epidemiological and genomic data of the Oropouche virus from regions outside the Amazon Basin. By generating 133 whole genome sequences from various regions across Brazil, the study doubles the number of publicly available genomes. Our findings reveal the virus movement over the past few years across Brazil, highlighting a north-south spatial trend from regions of historic endemicity to regions with clear epidemic potential. We identify 21 recombinant events, of which the potential for adaptation and the emergence of novel viral phenotypes remains possible but unclear. This study also reports the first fatal cases of Oropouche virus infection in patients without underlying relevant comorbidities, underscoring the public health risk of future outbreaks and the need for increased awareness and surveillance. Implications of all the available evidenceThe rapid spread of the Oropouche virus beyond the Amazon Basin into regions of Brazil further away than 3500 Km, coupled with the identification of genome recombinant events, raises the possibility that the virus is adapting to the new environments of its increasing spatial landscape. This evolution could lead to the emergence of new viral phenotypes, with potential changes at various levels, from vector efficiency, to disease outcome, raising the challenge of managing future outbreaks. The evidence underscores the critical need for enhanced surveillance systems at national and continental levels, in particular in urban centers which appear to have been particularly hit during the spatial expansion, to detect and respond to Oropouche virus outbreaks promptly.