Oropouche virus infected millions more than official data shows

The recent Oropouche virus outbreak in 2023 drew attention in Brazil and other Latin American countries not only because of its scale – with more than 30,000 cases recorded nationwide – but also because of the first confirmed death in the country caused by the disease and its rapid spread to all states, extending beyond the Amazon region. In light of this situation, the World Health Organization (WHO) expressed concern earlier this year and called for the accelerated development of prevention and control tools against this pathogen, which was virtually unknown until then.

Two studies published in the journals Nature Medicine and Nature Health have shown that the impact of the Oropouche virus is much greater than official data suggests. Using mathematical calculations, historical data, and blood bank analysis, the researchers estimate that since 1960, the virus has infected approximately 9.4 million people in Latin America and the Caribbean. In Brazil alone, there have been approximately 5.5 million cases.

The disease causes fever and symptoms similar to dengue. It can lead to serious complications, including neurological problems such as meningitis and meningoencephalitis, and microcephaly in cases of mother-to-fetus transmission.

We're facing a disease of much greater magnitude than previously imagined, which requires greater attention. We estimate that one in every thousand diagnosed cases progresses to serious complications such as neurological disorders, microcephaly, miscarriages, and liver complications, raising the priority level for public health."

José Luiz Proença Módena, coordinator of the Laboratory for the Study of Emerging Viruses (LEVE) at the State University of Campinas (UNICAMP) and co-author of the studies

The research was funded by the National Council for Scientific and Technological Development (CNPq), which is affiliated with Brazil's Ministry of Science, Technology, and Innovation; the Todos Pela Saúde Institute; the U.S. National Institutes of Health (NIH); and the British philanthropic organization the Wellcome Trust.

Manaus, the epicenter of the crisis

An estimated 300,000 people in Manaus, the largest metropolis in the Amazon region, were infected between 2023 and 2024 – nearly 260 times more than the number of confirmed cases. According to the researchers, the prevalence of antibodies against the virus increased from 11.4% in November 2023 to 25.7% in November 2024, indicating widespread transmission of the disease.

"The capital of the state of Amazonas is a city with over two million inhabitants and is considered the gateway to the Amazon region. The striking underreporting occurred due to several factors, mainly because the virus circulated silently before reaching the outskirts of the urban center, with many cases being asymptomatic or mild and going undiagnosed," says William de Souza, a professor at the University of Kentucky in the United States and co-author of the study.

This helps explain how the virus spread across all Brazilian states and neighboring countries, prompting the WHO to issue an international alert.

As for patients in remote regions of the Amazon, the researchers highlight the dynamics and logistics of the region. "Patients in remote regions of the Amazon often face travel times of more than 24 hours to reach a healthcare facility. That means that many cases likely went undiagnosed, allowing the virus to circulate silently until it reached the outskirts of a major urban center," Souza says.

The researchers found that the Oropouche virus circulates continuously, though often at levels so low that it becomes nearly undetectable by standard surveillance systems. "In our study, we identified two major Oropouche virus outbreaks in the Amazonian capital: one in the 1980s and one in 2023. Each one infected more than 12% of the population," says Módena.

The researchers also found that individuals infected in the 1980s could still neutralize the recent viral strain. "That suggests long-lasting cross-protection, which could inform future vaccination strategies," Souza explains.

A bush virus

The reemergence of the Oropouche virus in 2023 confirmed its spread across the country. The state of Espírito Santo had the highest cumulative rate, with 318 cases per 100,000 people. Meanwhile, the Southeast region accounted for 57.9% of reported cases, becoming the new epicenter of the disease.

Unlike other better-known arboviruses, the Oropouche virus is transmitted by the gunpowder midge (Culicoides paraensis), causing the disease to be 11 times more prevalent in rural areas than in cities.

"Unlike Aedes aegypti [the mosquito that transmits dengue, Zika, and chikungunya], which breeds in standing water, the gunpowder midge lays its eggs in moist soil rich in organic matter. It's a bush mosquito found in humid areas. That's why cases are predominantly found in rural rather than urban areas," Souza explains.

"Historically, this disease was closely linked to areas with banana and cocoa plantations, but by studying the ecology of the virus, we found that the issue isn't the fruit itself but rather the ideal conditions of moist soil rich in organic matter. High temperatures and rainfall are also conducive to the spread of the midge," says the researcher.

The authors emphasize that the rural nature of the disease affects public policy strategies. "Combating the disease is very different from other mosquito-borne arboviruses, which are more urban. Strategies such as fumigation in squares and on paved streets are likely ineffective against Oropouche. The gunpowder midge doesn't live in household drains but rather in the humidity of forested areas and the vegetation on the outskirts of cities," Souza explains.

Another important characteristic of the midge is that it is three times smaller than a common mosquito – an ideal size for getting through mosquito nets. However, the reason behind this aggressive resurgence lies not only in the climate but also in a new viral recombination, or reassortment.

In their study, the researchers identified a new viral lineage resulting from genetic reassortment, which occurs when two different viruses infect the same cell. This increases the replication capacity of the virus and makes it harder for antibodies from previous infections to neutralize it. This means the pathogen is better suited for further territorial expansion (read more at agencia.fapesp.br/52456). 

"The reemergence of Oropouche shows us that we can't combat all arboviruses with the same approach because the gunpowder midge doesn't follow the same rules as Aedes. That makes current surveillance against the Oropouche virus insufficient and drastically underestimates the true scale of the disease," says Módena.

In his view, surveillance must extend beyond major cities. "Although long-term immunity appears to exist for those who have already been infected, the speed with which the virus has spread across all Brazilian states shows that the healthcare system needs new detection systems, including those focused on surveillance far from major urban centers," he states.

The researchers emphasize the need for structural changes, such as adopting continuous serological studies, using blood banks as an early warning system, and integrating digital and genomic tools to track outbreaks and mutations. They also stress the importance of decentralizing laboratory testing and establishing active, permanent surveillance that can combine environmental, serological, and genomic data to anticipate risks and guide vaccination strategies.