For the first time, scientists have tracked the dispersion of the Oropouche virus in the Brazilian Amazon region, an important first step to control future outbreaks of a disease with more than 100,000 reported cases since the 1960s.

The researchers followed a new genetic variant of the virus, and showed that it spread through the movement of both insect vectors and humans, according to the study, “Human Outbreaks of a Novel Reassortant Oropouche Virus in the Brazilian Amazon Region,” which published Sept. 19 in Nature Medicine.

“Until recently, the virus was mostly contained around the Amazon River,” said Ana Bento, assistant professor in the Department of Public and Ecosystem Health in the College of Veterinary Medicine, and co-author of the paper. “In 2023-24, we started to see the pathogen spread in other areas in Brazil. We also started to see a higher magnitude of cases, from a few hundred to a few thousand.”

Oropouche virus is primarily transmitted by midges, and potentially mosquitoes, which infect vertebrates including sloths, monkeys, rodents and birds. Humans are not a necessary part of the virus’s life cycle, but occasional spillovers from wildlife to humans can trigger outbreaks. With more than 6,000 cases recorded in the 2023-24 season alone, the current epidemic is the largest recorded in the 21st century.

People infected with the virus present fever, severe headache, muscle and joint pain, with 4% of patients developing severe neurologic symptoms – similar to dengue, Zika and chikungunya. Because of this similarity, Oropouche infections are often misdiagnosed and, according to Bento, the number of Oropouche cases has probably been historically underestimated.

Patients are typically first tested for dengue. “When they were negative, they were tested for other viruses, and we found that lot of them were Oropouche cases,” Bento said. 

With increased number of Oropouche cases and wider geographical spread, the researchers suspected something was different with the virus this season. Among the 6,000 confirmed positive cases, the researchers sequenced the genetic material of 382 viruses. They found these cases carried a variant of the virus that had never been seen before.

In this study, scientists have not established if the new genetic rearrangement of the virus’ genetic material is associated with its ability to disperse or infect its hosts. However, its unique genetic signature allowed the study’s authors to track the spread of the new variant.

They discovered that the virus had two types of dispersion patterns: a short-distance one, consistent with the flight range of the midges, and a longer-distance dispersion, attributed to humans’ movement. Infected people travel and get bitten by midges and mosquitoes at their next destination, thus passing the infection to new insects, and eventually human populations in these new regions. 

Since early 2024, dozens of cases of local transmission of the Oropouche virus were recorded in Brazil outside the Amazonian states, highlighting the risk of a wider viral dissemination.

“It’s a worrying trend that these diseases are more spread out,” Bento said. She is also concerned that, in the context of climate change and warmer environments, “these vectors and pathogens will have new environments to survive and invade, like the Southern states in the U.S.”

As of 2024, a few dozen cases of the Oropouche virus have been recorded outside Brazil, including cases brought by travelers to Europe and the United States.

“The point of this study was to document the genetic change and the speed of the spread,” Bento said. “This is the first of many studies to come.”

For epidemiology studies, she said, mathematical models will need to incorporate all three factors – virus, vector and host – to fully understand the virus’s dispersion. This is how researchers will get a more targeted vector control strategy and start searching for cases earlier, Bento said.

“We also need more Oropouche-specific campaigns,” she said. “We need to understand to true burden of the disease.”

Elodie Smith is a writer for the College of Veterinary Medicine.