The recent death of South American sea lions (Otaria flavescens) off the coast of Santa Catarina as a result of influenza A virus (H5N1) has raised alarm bells among researchers and public health authorities. A study published at the beginning of July in the scientific journal BMC Veterinary Research provides evidence of the avian influenza virus’s adaptation to mammals, with the possibility of intraspecies transmission. In light of this, the Butantan Institute has submitted a request to the National Health Surveillance Agency (ANVISA) for authorization to begin a clinical trial for a vaccine to protect against the disease.
“This virus found in sea lions may be able to bind to mammalian and avian receptors through the molecular markers we have identified,” says veterinarian Helena Lage Ferreira, from the University of São Paulo (USP), one of the study’s authors. “This is a major concern, because the virus is increasingly adapted to mammals and is becoming more virulent.”
Ferreira is part of a network of researchers that monitors stretches of the Brazilian coastline in partnership with the Brazilian Institute for the Environment and Renewable Natural Resources (IBAMA). This monitoring led to the identification of seabird deaths on beaches in the Southeast and in Santa Catarina. In October of the same year, there was a sudden increase in sea lion mortality off the coast of Santa Catarina.
At that time, teams from the University of Vale do Itajaí (UNIVALI) who are part of the Santos Basin Beach Monitoring Project, coordinated by IBAMA, collected tissue samples from the digestive and respiratory tracts of these animals to investigate the presence of H5N1—the avian influenza virus multiplies better in these cells. They also collected samples from the cloacas of 190 seabirds using a swab to analyze potential transmission between birds and mammals in the same area.
In all, the study included 17 different species, extracting total RNA and testing for the virus. By comparing the genome of the virus found in Santa Catarina sea lions and others from South America, the authors identified mutations in the viral genome that can cause changes in proteins responsible for viral replication in mammalian cells.
“When we shared the virus with the UN Food and Agriculture Organization (FAO), we realized that the genetic sequences we found were very close to those of sea lions from the Falkland Islands in Argentina,” highlights the researcher, who currently chairs the Brazilian Society for Virology. But they are not identical, which suggests an evolutionary process.
This finding suggests transmission between sea lions—and no longer just from birds to these mammals, as had been previously documented. It is the first sign of this virus spreading in wild animals. A study published in July in Nature journal by Brazilian veterinarian Leonardo Caserta, of Cornell University, in the United States, suggests transmission among cattle in the US.
“This indicates that there is what we call microevolution of the virus. It keeps evolving within mammal species; we did not find these same mutations in birds,” stresses virologist Fernando Spilki, of Feevale University, in Rio Grande do Sul, and coordinator of the National Institute of Science and Technology (INCT) in Genomic Virus Surveillance and Single Health. “It is now more difficult to say that each and every single case in mammals was an avian infection.”
Chilean veterinary virologist Victor Neira, of the University of Chile, agrees. “We weren’t sure if the virus we started seeing here in Chile was already being transmitted among sea lions, but after it spread in the Atlantic, with this new finding in Brazil and data from Argentinian and Uruguayan groups, it’s clear that it’s the same virus,” he told Pesquisa FAPESP. He is one of the authors of a study on the mortality of sea lions off the Chilean coast, published in October 2023 in the journal Veterinary Quarterly.

H5N1 overview
In addition to sea lions, the World Organisation for Animal Health (WHOA) website documents cases of avian influenza in seals, otters, foxes, bears, raccoons, cats, dogs, and goats, among other mammal species—including humans. In 2023, the virus was responsible for a mass die-off of southern elephant seals (Mirounga leonina) in Argentina, particularly pups. Recently, in the United States, H5N1 was detected in the raw milk of infected dairy cows. But US health officials claim that pasteurization appears to inactivate the virus, making the milk safe for consumption.
According to the Brazilian Ministry of Agriculture, Livestock, and Food Supply (MAPA), the first case of H5N1 in Brazil was recorded in May 2023. Since then, 3,160 cases have been investigated and there has been no confirmation of infection in commercial poultry, which could have a significant impact on the national economy and public health (see infographic). To date, no human cases have been reported, the Ministry of Health said in a statement.
Since 2003, almost 900 human cases have been reported to the World Health Organization (WHO). That year, the virus, detected in China in 1996, resurfaced and spread among birds in several Asian countries. In 2021, a new variant of H5N1 emerged in Europe and spread around the world. Over the past 20 years, 24 countries have documented occurrences. Symptoms of H5N1 infection can include high fever, malaise, cough, sore throat, muscle pain, and conjunctivitis. Sometimes the infection progresses to a severe respiratory illness and neurological changes, such as altered mental state or seizures.

The common tern (Sterna hirundo) is one of the seabirds affected by H5N1Simbem / iNaturalist
Pandemic potential
According to virologist Paula Cristina Resende, of the Oswaldo Cruz Institute’s Laboratory of Respiratory Viruses, Exanthematics, Enteroviruses and Viral Emergencies (IOC-FIOCRUZ), when the influenza A H5 virus is identified in other species, especially mammals, it sends out a warning signal to public authorities. “We can never let our guard down with this virus,” the researcher explains. “H5N1 always has pandemic potential because it is a new virus for the human population’s immune memory. Influenza A viruses can undergo point mutations and gene rearrangements, which can lead to the emergence of new viral subtypes.” However, she emphasizes that there is a global surveillance network that has been well implemented since 1952, coordinated by the WHO, with about 160 laboratories in 129 countries, including three in Brazil.
In addition to surveillance, Resende emphasizes that it is important for the country to have a stockpile of the antiviral drug Oseltamivir, which is effective against H5N1, as well as a vaccination strategy. “Having a stockpile of vaccinations with pre-pandemic H5N1 seed viruses would help us to quickly begin immunizing vulnerable populations and mitigate the possible spread of the virus.”
The Butantan Institute, in São Paulo, has begun production of a vaccine against the disease. In a statement, the institute said that tests are being conducted with vaccine strains provided by the WHO, and that the first pilot batch is ready for preclinical testing, which precedes human trials. Testing is currently underway to assess the vaccine’s therapeutic potential and safety. The Butantan Institute is eager to be fully prepared and has already conducted animal trials for vaccines produced from the strains provided by the WHO. Once it receives approval from ANVISA, it will begin clinical trials for a vaccine against the H5N8 virus, chosen for its ability to cause severe symptoms and even death. The first step, if approved, will be to test a few volunteers to assess safety and the ability to generate antibodies. Progressing with clinical trials could enable a strategic stockpile should the need arise, says the Butantan press office. The H5N1 strain was also tested in the preclinical study and could be used if this variant spreads in the human population.
To avoid being infected with the H5N1 virus, people are advised to not touch sick or dead wild birds or sea lions. When walking pets, ensure that dogs do not touch them either. In addition to these measures, if you see a sick bird or sea lion, you are advised to notify the Brazilian Veterinary Service via the internet.
The story above was published with the title “Bird flu in mammals” in issue 343 of September/2024.
Project
Korea-Brazil joint research program on highly relevant animal diseases, using avian influenza as a model (n° 23/08501-0); Grant Mechanism Regular Research Grant; Agreement NRFK-FAPESP; Principal Investigator Helena Lage Ferreira (USP); Investment R$169,103.48 + US$15,681.00.
Scientific articles
ARAUJO, A. de C. et al. Mortality in sea lions is associated with the introduction of the H5N1 clade 2.3.4.4b virus in Brazil October 2023: Whole genome sequencing and phylogenetic analysis. BMC Veterinary Research. Vol. 20, 285. July 2, 2024.
CASERTA, L. C. et al. Spillover of highly pathogenic avian influenza H5N1 virus to dairy cattle. Nature. Online. July 25, 2024.
ULLOA, M. et al. Mass mortality event in South American sea lions (Otaria flavescens) correlated to highly pathogenic avian influenza (HPAI) H5N1 outbreak in Chile. Veterinary Quarterly. Vol. 43, no. 1, pp. 1–10. Oct. 19, 2023.