Until recently, almost no one had heard of the "Oropouche virus." But after a large-scale outbreak swept through Brazil in 2023, the virus, which was originally limited to the Amazon Basin, quickly attracted international attention: tens of thousands of people were infected, the country's first death occurred, and spread beyond traditional endemic areas.

The World Health Organization subsequently called for the rapid development of new surveillance, prevention and control tools. Two recent studies published in Nature Medicine and Nature Health show that the actual number of infected people is much higher than official reports. The research team estimated through mathematical model deduction, historical data analysis and blood bank sample testing that since 1960, approximately 9.4 million people in Latin America and the Caribbean have been infected with Oropouche virus, of which approximately 5.5 million cases may have occurred in Brazil.

The disease causes symptoms such as fever, with clinical manifestations similar to dengue fever. In some patients, Oropouche virus can cause serious complications, including neurological diseases such as meningitis and meningoencephalitis; it can also cause microcephaly when the virus is transmitted from mother to fetus. José Luiz Proença Módena, one of the study leaders and coordinator of the Laboratory for Research on Emerging Viruses (LEV) at the State University of Campinas, said: "The scale of the disease we are facing is much greater than previously understood, which requires a higher level of attention. We estimate that one in every thousand confirmed cases develops serious complications, including neurological disorders, microcephaly, miscarriage, and liver damage, which significantly raises its public health priority."

Manaus, the largest city in the Amazon region, has become the "epicenter" of the crisis. Research shows that between 2023 and 2024, about 300,000 people locally will be infected with the Oropouche virus, which is almost 260 times the official number of confirmed cases. Serological survey results show that the proportion of Oropouche virus antibody positive among Manaus residents increased from 11.4% in November 2023 to 25.7% in November 2024, highlighting the widespread and sustained spread of the virus in the local area.

William de Souza, a co-author of the study and a professor at the University of Kentucky in the United States, pointed out that there are multiple reasons for serious underreporting, the most important of which is the long-term "silent epidemic" of the virus before reaching the edge of the city: a large number of cases are asymptomatic or mild, and laboratory confirmation cannot be obtained. This transmission pattern helps explain how the Oropouche virus spread throughout Brazil and across borders into neighboring countries, ultimately prompting the WHO to issue an international alert.

In remote areas of the Amazon, epidemic prevention and control face even more severe practical difficulties. Patients often take more than 24 hours to arrive at a medical facility, which means that a large number of cases are not detected early in the course of the disease, and the virus can "hidden circulation" in urban-rural fringes and small communities for a long time. The research team found that Oropouche virus can spread in the population at low levels and persistently, often below the detection threshold of conventional surveillance systems. In Manaus, researchers identified two large outbreaks - one in the 1980s and another in 2023, both of which infected more than 12% of the local population.

It is worth noting that some people infected in the 1980s are still able to neutralize the current new generation strain, which suggests that the virus may induce longer-term cross-protective immunity and provide important clues for future vaccine strategies.

Research also shows that the resurgence of the epidemic in 2023 confirms that Oropouche virus has spread widely in Brazil. Espiritu Santo state reported the highest cumulative incidence rate, recording 318 cases per 100,000 people. The southeastern region of Brazil became the new reporting center, accounting for approximately 57.9% of the country's cases.

Different from the more well-known arboviruses such as dengue fever, the vector of Oropouche virus is not Aedes mosquitoes, but microscopic midges (scientific name: Culicoides paraensis) commonly known as "gunpowder midges". Studies show that the incidence of the disease in rural areas is 11 times higher than in cities. Souza pointed out that Aedes mosquitoes prefer to breed in stagnant water environments, while gunpowder midges lay their eggs in moist soil rich in organic matter, making them a typical "jungle blood-sucking insect", more common in moist woodlands and vegetation around cities than in concrete streets and household sewers. In addition, gunpowder midges are about one-third the size of ordinary mosquitoes and are large enough to pass through common mosquito net holes, which also objectively increases the risk of transmission.

The research team emphasized that the ecological characteristics of this "jungle virus" mean that traditional urbanization prevention and control strategies - such as large-scale fumigation of squares and paved streets - have limited effectiveness against Oropouche virus. They also pointed out that the violent rebound of this round of epidemic is not only related to climate, but also to the genetic reassortment (recombination) of the virus itself.

In the latest research, scientists discovered a new virus lineage resulting from genetic "reassortment". This process occurs when two different viruses co-infect the same cell, and the gene segments are recombined during replication. This mechanism can increase the efficiency of virus replication and reduce the neutralizing ability of antibodies formed after previous infection, thereby helping the pathogen adapt to the new ecological environment and spread to new areas.

Módena pointed out that the re-emergence of Oropouche virus shows that prevention and control cannot be carried out in the same way as other arboviruses, because the ecology and behavior of Oropouche vectors are completely different from those of Aedes mosquitoes. The current city-focused surveillance system clearly does not adequately reflect the true scale of the disease, leading to widespread underreporting and underestimation of risk. He also emphasized that although previously infected people may acquire long-term immunity, the fact that the virus is spreading rapidly in all Brazilian states shows that the health system urgently needs to build a more sensitive and wider-coverage testing network, especially to strengthen surveillance capabilities away from large urban areas.

The research team called for a structural reshaping of the Oropouche virus surveillance system and put forward a number of specific suggestions: carry out continuous serological surveys, incorporate blood bank samples into the "early warning" system, introduce digital monitoring and genome sequencing tools to track outbreaks and virus mutations, and promote laboratory testing from big cities to grassroots areas, and build an active and normalized surveillance network that integrates environmental data, serological data and genomic data. These measures aim to identify risks in advance, provide a basis for vaccine development and immunization strategies, and prevent this "neglected virus" from quietly breaking through the global public health defense line in the future.