Research led by Fiocruz has shown that the recent outbreak of Oropouche fever in the Amazon region, the widest ever recorded, was caused by a new viral strain, called 'OROV BR-2015-2024'. The peer-reviewed article was published in the prestigious international scientific journal Nature Medicine on an accelerated basis to allow early access to the findings. The final edited version of the paper will soon be published in the journal. Previously, as a way of communicating the results of the research to the scientific community, the study was published in a preliminary version on the medRxiv preprint platform, which does not have a peer review process.
The study analyzed samples from 382 cases recorded between August 2022 and February 2024 in the states of Amazonas, Acre, Rondônia and Roraima. During this period, more than 6,000 cases were recorded in 140 municipalities in the Northern Region. The analyses revealed that the infections were caused by a new strain of the Oropouche virus, which was also detected in a sample collected in the city of Tefé, in Amazonas, in 2015, and in French Guiana, in 2020.
Considering the genetic characteristics of the pathogen, the researchers believe that the 'OROV BR-2015-2024' strain probably emerged between 2010 and 2014 in the state of Amazonas, spreading silently until it caused the recent epidemic.
Researchers from Fiocruz units in five states collaborated on the study: the Oswaldo Cruz Institute (IOC/Fiocruz), in Rio de Janeiro; the Leônidas and Maria Deane Institute (Fiocruz Amazônia), in Amazonas; Fiocruz Rondônia; the Aggeu Magalhães Institute (Fiocruz Pernambuco) and the Carlos Chagas Institute (Fiocruz Paraná).
The work also included cooperation from the Central Public Health Laboratories (Lacens) of Amazonas, Acre, Rondônia, Roraima and Paraná; the Acre State Health Department (Sesacre); the General Coordination of Public Health Laboratories (CGLab) and the General Coordination of Arbovirus Surveillance (CGArb) of the Ministry of Health; the Evandro Chagas Institute (IEC), the Federal Universities of Amazonas (Ufam), Espírito Santo (Ufes) and Pernambuco (UFPE); the Amazonas State University (UEA); the Global Data Science Initiative (Gisaid) platform; as well as the Universities of California and Cornell, in the United States.
Genetic rearrangement
Leader of the research, virologist Felipe Naveca explains that the new strain of the Oropouche virus emerged through a genetic rearrangement between strains circulating in Brazil and another circulating in Peru, Colombia and Ecuador. "The new strain arose from an evolutionary event that we call a genetic rearrangement. This occurs when the same person or animal is infected by two different viral strains simultaneously. Thus, in the process of viral replication, a strain can emerge that is a combination of two pathogens, as we observed in this case", details Naveca, who is head of the Laboratory of Arboviruses and Hemorrhagic Viruses at the IOC and coordinator of the Center for Surveillance of Emerging, Re-emerging or Neglected Viruses at Fiocruz Amazônia.
According to the scientists, further research is still needed to determine the impact of the emergence of the new strain on the spread of Oropouche fever in the Amazon and beyond. On the one hand, the new strain has alterations to the surface of the viral particle that could facilitate the escape of antibodies. Therefore, people previously infected with the Oropouche virus may have reduced protection against the new strain. Additionally, a preliminary study, carried out by another group of scientists and not yet peer-reviewed, indicates that the new strain replicates faster in cells than the first strain of the Oropouche virus isolated in Brazil in the 1960s.
On the other hand, the researchers note that the new strain circulated for almost ten years before causing a major outbreak. In this context, the scientists draw attention to the impact of extreme weather events and environmental degradation on the transmission of the Oropouche fever.
"An epidemic situation is usually multifactorial. There is a new strain, which has succeeded in spreading. However, this cannot be attributed solely to a virtue of the virus. We have a context of climate change and deforestation, which affect the behavior of the vector and have most likely contributed to the population's greater exposure to the virus," Naveca said.
The article published in Nature Medicine points out that the recent outbreak of Oropouche, between 2022 and 2024, was preceded by record floods in the Amazon associated with the La Niña weather phenomenon, which, unusually, lasted from 2020 to 2023. The region then suffered record droughts and heat during the transition to the El Niño phenomenon.
The advance of deforestation in the Amazon since 2018 may also have contributed to the spread of the disease. The highest incidence of the Oropouche fever was observed in the region called Amacro, which combines municipalities in Amazonas, Acre and Rondônia, where most of the forest loss occurred between 2017 and 2021. In Roraima, municipalities close to the most critical areas of deforestation also concentrated infections.
Displacement of the virus
The study confirmed the seasonal pattern of the Oropouche fever. According to the scientists, a high spread of the virus was observed in the rainy seasons and low, albeit persistent, transmission in the dry seasons. This pattern can be explained by the greater proliferation of the disease vector during the rainy season, since the insect Culicoides paraensis, popularly known as the maruim or gunpowder mosquito, breeds in environments with moist organic matter.
By analyzing the genetic characteristics of the viruses and the locations where cases were recorded, the researchers observed that the spread of the disease occurred through a combination of the displacement of vectors and infected humans. In around two thirds of the cases, the spread of the virus was compatible with the insects' flight range, which was below 2 km per day. However, in approximately one third of the records, a dispersion of more than 10 km per day was observed, indicating an association with human displacement.
Importance of surveillance
The sequencing of a large number of complete genomes was one of the strengths of the research. The amount of 382 sequences decoded in the study is five times greater than the total that was previously available in databases, which had around 70 deposited genomes. The protocol for genetic sequencing of the Oropouche virus, developed by the scientists, could facilitate the work of genomic surveillance of the pathogen in Brazil and other countries.
The importance of monitoring the disease is emphasized by the scientists, who point out that it was only last year that the country began to systematically diagnose cases of Oropouche. Developed by Fiocruz Amazônia, a protocol for detecting the Oropouche and Mayaro viruses has been implemented in all Lacens by the Ministry of Health.
"We need to remain vigilant in order to understand the epidemiological situation in the country. In a year with more than six million cases of dengue, around eight thousand cases of Oropouche fever would go unnoticed if there were no laboratory diagnosis, because the symptoms of the two diseases are very similar," Naveca comments.
"We are living in a context of climate change and deforestation, which is altering ecological niches and changing the behavior of vectors and other animals. It is essential to be alert to detect emerging diseases such as Oropouche," adds the virologist.