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

The researchers followed a new genetic variant of virusand 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 was is published 18 September in Natural medicine.

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

Oropouche virus is primarily transmitted by mosquitoes, and potentially mosquitoes, which infect vertebrates including sloths, monkeys, rodents and birds. Humans are not a necessary part of the virus life cyclebut 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 have fever, severe headache, muscle and joint painwith 4% of patients developing severe neurological 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 underestimated historically.

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

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

In this study, researchers have not determined whether the new genetic rearrangement of the virus genetic material is associated with its ability to spread or infect its hosts. But 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 spread patterns: a short-distance pattern, consistent with the mosquito’s flight range, and a longer-distance spread pattern, attributed to human movement. Infected people travel and are bitten by mosquitoes and midges at their next destination, thereby transmitting the infection to new insects and eventually human populations in these new regions.

Since the beginning of 2024, dozens of cases of local transmission of the Oropouche virus have been recorded in Brazil outside the Amazon, indicating the risk of a wider spread of the virus.

“It is a worrying trend that these diseases are more widespread,” 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, such as the southern states of the United States”

As of 2024, a few dozen cases of the Oropouche virus have been recorded outside of Brazil, including cases from 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 epidemiological studies, she said, mathematical models will need to incorporate all three factors — virus, vector and host — to fully understand the spread of the virus. 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 the true burden of the disease.”