A new study uncovers how Oropouche virus is breaking out of the Amazon, spreading across Brazil and beyond. Scientists warn that environmental changes, human mobility, and viral evolution are driving its rapid expansion—raising urgent concerns for global public health.
Study: Travel-associated international spread of Oropouche virus beyond the Amazon. Image Credit: CI Photos / Shutterstock
Oropouche virus (OROV), historically confined to the Brazilian Amazon Basin, has caused multiple outbreaks across many Brazilian states since 2022. Many OROV cases have also been detected beyond Brazil in recent times.
Researchers have conducted whole-genome sequencing of viral isolates collected from outbreak regions to understand the dynamics of viral transmission to non-endemic regions. The study is published in the Journal of Travel Medicine.
Background
Oropouche virus (OROV) is an arthropod-borne, single-stranded, negative-sense RNA virus segmented into three parts: small, medium, and large. These three segments encode essential components required for viral growth, transmission, and infectivity.
After its first detection in Trinidad and Tobago in 1955, the virus has caused several outbreaks among animals (non-human primates, sloths, and birds) in the Amazon Basin. In humans, the virus is primarily transmitted by midges (Culicoides paraenesis) and causes mild to moderate infections that resolve within a week.
Up until August 2024, approximately 30 outbreaks have been reported in Latin America. However, recent epidemiological data demonstrates a sharp increase in OROV cases across multiple non-endemic Brazilian states, with travel-related cases reported in Italy, Spain, and Germany originating from travelers who visited Cuba.
The first three fatal cases of OROV infection have also been reported in Brazil in 2024. All these reports highlight the spread of the virus outside the Amazon and raise concerns among public health authorities.
Study Design
Researchers conducted whole-genome sequencing of OROV-infected patient-derived samples collected from five Brazilian states between February and May 2024. They selected the samples for genomic analysis based on the available clinical and epidemiological metadata.
They generated 133 whole-genome sequences covering the virus’s three genomic segments: the small, medium, and large segments. These sequences included the first genomes from regions outside the Amazon and from the first recorded fatal cases.
Study Findings
The study reported a sharp rise in OROV infections in humans in the western Amazon region between late 2022 and early 2024. This induction coincided with a surge in OROV testing frequency (from 238 tests in 2020 to 54,428 in early 2024) across the country, indicating intensified surveillance efforts.
The phylogenetic analysis revealed that the new viral sequences generated in the study share a common ancestor with sequences obtained from the Amazon Basin sampled since 2022, suggesting a possible Amazonian origin of the recent viral lineage.
Because of its segmented pattern, the OROV genome is likely to undergo reassortment and recombination events. The study identified 21 reassortment events (including 17 S-M, 7 S-L, and 11 M-L reassortments). However, whether these genomic changes have facilitated viral adaptation to local ecological conditions or contributed to its infectivity and pathogenicity remained unclear.
By conducting a phylogeographic reconstruction of the 2022–2024 Brazilian dataset together with recently isolated international genome sequences from Peru and Italy, the study found a rapid north-to-south viral transmission within Brazil, followed by cross-border transmission into Peru.
The study also found that OROV cases reported in Italy are associated with travelers who returned from Cuba. However, Cuban cases are inferred solely from travel history, as genomic data from Cuba itself are unavailable, limiting definitive conclusions about transmission routes. These observations highlight the role of human mobility in viral spreading.
Study Significance
The study demonstrates how OROV evolution through genomic reassortment has facilitated its rapid transmission within and beyond Brazil. The findings indicate that the 2022–2024 lineage of OROV might have emerged in central Amazonas between 2010 and 2014, with evidence of long-term cryptic circulation in the Amazon during the late 2010s due to limited surveillance.
The study’s north-to-south viral movement coincides with the Amazon Basin’s rainy season. Existing eco-epidemiological studies suggest that OROV preferentially circulates in regions with high population density, favorable climatic conditions, and reduced evergreen broadleaf forest cover.
Furthermore, deforestation, urbanization, and agricultural practices (e.g., banana and cocoa farming) facilitate midge breeding, increasing the risk of viral transmission and shaping the virus’s geographical range.
The detection of the first three fatal OROV cases in young adults without comorbidities —including mutations in the M (I13V, M642I) and L (T857A) segments— highlights the need for further investigations, with a particular focus on vertical transmission and pregnancy outcomes.
The Brazilian Ministry of Health has recently reported the first fetal death due to OROV with mother-to-child transmission in Pernambuco. However, asymptomatic or mild cases may be underrepresented in genomic datasets, biasing surveillance efforts. This highlights the need to identify viral factors associated with severe outcomes and develop effective interventions.
The study identified travel-related OROV cases, which indicate that human mobility plays a vital role in viral spreading beyond Brazil. Key limitations include the lack of genomic data from Colombia, Cuba, and other affected countries, preventing a complete understanding of transmission networks.
Overall, the study highlights the urgency for continuous genomic surveillance to understand the evolutionary and epidemiological dynamics of OROV. This is particularly important for preventing future outbreaks and ensuring timely public health responses.