Oropouche virus: 200-fold increase in infections this year in Brazil compared to the last decade due to novel variant

Brazilian researchers publish preliminary data showing that the pathogen has undergone mutations making it more aggressive and contributing to resurgence of the disease in Brazil since 2023.

By Julia Moióli  |  Agência FAPESP – The current outbreak of oropouche fever is caused by a novel variant of the arbovirus (OROV) that can replicate up to 100 times more than the original while also evading the victim’s immune response, according to an article published as a preprint (not yet peer-reviewed) on medRxiv.

Oropouche fever is a neglected tropical disease endemic to Latin America and the Caribbean. It is transmitted by mosquitoes and Culicoides midges. The main symptoms are headache, joint and muscle pain, nausea, vomiting, fever, chills, and photophobia. Some patients may manifest more severe symptoms, such as bleeding, as well as complications including meningitis and meningoencephalitis.

Although the disease has been documented in South America since the 1950s, the number of cases increased sharply between November 2023 and June 2024 in Brazil, Bolivia, Colombia and Peru. Autochthonous infections were detected in previously non-endemic areas throughout Brazil, with reports of cases in 21 states and a nearly 200-fold increase in incidence compared with the 2010s.

To investigate the virological factors that have contributed to this heightened spreading of oropouche fever, researchers at the State University of Campinas (UNICAMP), the University of São Paulo (USP) and the Federal University of Manaus (UFAM) in Brazil, collaborating with colleagues at the University of Kentucky in the United States, analyzed genomic, molecular and serological OROV data for the period between January 1, 2015, and June 29, 2024. They also characterized the variant in vitro and in vivo. The research was funded by FAPESP (projects 18/14389-0, 2022/00723-1, 2022/10408-6 and 2023/11521-3).

The first step consisted of PCR testing of serum samples from 93 patients in Amazonas state with unidentified acute fever between December 2023 and May 2024. The results were positive for OROV in 10.8%. 

Next, the researchers assessed the virus’s capacity to replicate in different cells (from primates and humans), and the capacity of the antibodies to neutralize cellular infection using a plaque reduction neutralization test (PRNT50) that measures the reduction in the number of areas where the virus causes cell death.

“We found that the novel OROV replicated approximately 100 times more than the prototype, pointing to a much higher viral load” said Gabriel C. Scachetti, first author of the article and a researcher affiliated with UNICAMP’s Laboratory for Studies of Emerging Virus (LEVE). “In addition, it produced 1.7 times more plaques than the prototype, and plaque sizes were 2.5 times larger, also indicating higher virulence.”

“When we infected mice with the two strains, we found that the older virus didn’t protect them against the novel variant. The reduction in neutralization capacity was at least 32-fold,” said Julia Forato, second author of the article and also affiliated with LEVE.

Public health

“We present an overview of the oropouche epidemic with possible explanations for the rise in the number of cases. The study serves as a basis for action to implement epidemiological control,” said José Luiz Proença Módena, co-principal investigator for the project. He is a professor at the State University of Campinas’s Institute of Biology (IB-UNICAMP) and head of LEVE. “If the novel variant escapes protection in areas with high seroprevalence, infections and transmission are more likely, with dissemination to other parts of Brazil. We therefore need to confirm and monitor positive cases, using tools to reduce the risk of transmission. The outbreak is far from over. It could potentially wreak havoc in areas where the virus has never circulated before.”

Ester Sabino, full professor at the University of São Paulo’s Medical School (FM-USP), and William Marciel de Souza, assistant professor at the University of Kentucky, are also co-authors of the article.

The article “Reemergence of Oropouche virus between 2023 and 2024 in Brazil” is at: www.medrxiv.org/content/10.1101/2024.07.27.24310296v1.