CDC A(H5N1) Bird Flu Response Update March 19, 2025

Recent updates

Laboratory

• CDC completed serology testing on blood specimens from close contacts of a child with mild illness in San Francisco who was confirmed to be positive for avian influenza A(H5N1) virus, though, there were no known animal exposures associated with that case. Serology testing was conducted to look for antibodies to influenza A(H5N1) virus in this child, which would indicate recent infection. The child's blood was tested and found to have antibodies to avian influenza A(H5N1) virus. None of the close contacts of the case in San Francisco who were tested had antibodies to avian influenza A(H5N1) virus, which supports the conclusion that none of these close contacts were infected, and that no person-to-person spread occurred among these close contacts. These findings are reassuring. To date, human-to-human transmission of influenza A(H5) virus has not been identified in the United States.
• CDC has sequenced the virus from the most recent Ohio human case. Genetic data have been posted in GISAID (Epi ID 19785793) and have been submitted to GenBank. Sequencing indicates this is a clade 2.3.4.4b virus of the D1.3 genotype based on classification using USDA's genotyping assignment criteria. D1.3 viruses, like D1.1 viruses, originated from A3 genotype A(H5N1) viruses that were introduced to North America in 2022 and have subsequently reassorted with North American wild bird avian influenza viruses. There were no markers that would impact the effectiveness of influenza antivirals or existing candidate vaccine viruses. Finally, CDC did not identify changes that would make this virus better adapted to spread among or infect mammals. Attempts to isolate this virus in eggs are ongoing.

Publications

Pre-Existing Antibodies

Historically, the mortality rate from avian influenza A(H5N1) observed globally has been around 50%; however, only one of 70 human infections* in the United States to date has resulted in death. Recent studies have reported that ferrets previously infected with seasonal influenza A(H1N1) virus had less severe illness from H5N1 bird flu. While more study is needed, pre-existing antibodies could contribute to decreasing the severity of H5 bird flu illness in U.S. cases.

A CDC study published on February 21, 2025, in Emerging Infectious Diseases found that ferrets previously infected with seasonal influenza A(H1N1)pdm09 virus had developed cross-reactive antibodies to some components of an avian influenza A(H5N1) virus. When these ferrets were later exposed to an avian influenza A(H5N1) virus, they exhibited reduced viral replication and decreased onward spread of avian influenza A(H5N1) virus compared with ferrets that had not been previously infected with A(H1N1)pdm09 virus and did not have these cross-reactive antibodies. Overall, these findings in ferrets suggested that prior seasonal influenza virus infection with an A(H1N1)pdm09 virus may provide some level of protection against clade 2.3.4.4b avian influenza A(H5N1) viruses.

A second study, published on March 17, 2025, in The Lancet Microbe reported similar findings. Ferrets with antibodies from previous infection with the seasonal influenza A(H1N1)pdm09 virus [A/California/7/2009] that were later infected with avian influenza A(H5N1) virus had less severe illness and were less likely to spread the virus to other ferrets in the same enclosure compared to ferrets with no preexisting immunity to influenza virus. This study only looked at prior infection and did not look at the effects of prior vaccination in ferrets, so it's not possible to draw conclusions from this study on the potential effect seasonal flu vaccines might have on reducing severity of H5N1 bird flu illness in ferrets or in people; seasonal influenza vaccines are not designed or intended to prevent H5N1 bird flu disease. The study also found that when ferrets were exposed to an avian influenza A(H5N1) clade 2.3.4.4b virus [A/Texas/37/2024] via the surface of their eyes, they developed severe and transmissible disease just as they did after respiratory exposure, highlighting the importance of following recommendations for eye protection for people with exposure to animals infected or potentially infected with avian influenza A(H5N1) viruses.

Immune Response from Mild Illness

Another recent report, published on March 7, 2025, in Emerging Infectious Diseases assessed the immune responses of two dairy farm workers in Michigan who tested positive for H5N1 bird flu following work related exposure to infected dairy cows. One of the two workers, who reported having mild illness with symptoms like eye redness (conjunctivitis) had an immune response resulting in the development of neutralizing antibodies against avian influenza A(H5N1) virus. Clade 2.3.4.4b avian influenza A(H5N1) virus was isolated from this person. The other person did not develop neutralizing antibodies. This is the first study conducted in people to assess immunity to clinically mild illness from A(H5) virus infection. Prior to this study, limited data were available on immune responses to H5N1 bird flu among people with clinically mild illness like conjunctivitis.

Antiviral susceptibility

CDC regularly performs sequencing of seasonal influenza A and B viruses and novel influenza A viruses, including A(H5N1) viruses, to assess for genetic changes known to be associated with antiviral resistance. In a new CDC study published in Emerging Infectious Diseases on March 7, 2025, CDC scientists assessed the antiviral susceptibility of clade 2.3.2.1c A(H5N1) viruses and clade 2.3.4.4b A(H5N1) viruses collected from humans in Cambodia, United States, and Chile. The study found that except for two viruses isolated from humans in Cambodia, all viruses were susceptible to M2 ion channel-blockers in cell culture-based assays. All viruses were susceptible to the PA cap-dependent endonuclease inhibitor class of antiviral drugs, baloxavir and tivoxavir, and to the polymerase basic 2 (PB2) inhibitor antiviral drug, pimodivir. All viruses also displayed susceptibility to neuraminidase inhibitor class of antiviral drugs, which includes oseltamivir, zanamivir, peramivir, laninamivir, and AV5080. Oseltamivir was approximately 10-fold less active at inhibiting the neuraminidase activity of clade 2.3.4.4b viruses and approximately 3-fold less active against clade 2.3.2.1c viruses, when compared to seasonal influenza A viruses. The clinical significance of these laboratory findings, however, is unknown. Significant reduction in antiviral susceptibility is considered to be greater than 100-fold reduction. The laboratory findings in this study, therefore, indicate that these A(H5N1) viruses are likely to retain susceptibility to oseltamivir. Additionally, these findings do not support changing the current recommendations for antiviral treatment of human infections with novel influenza A viruses, including A(H5). CDC continues to recommend prompt treatment with oseltamivir for people with confirmed or suspected A(H5N1) virus infection. Flu antiviral drugs, including oseltamivir, work best when started as soon as possible, ideally within two days after flu symptoms begin.

* One additional case was previously detected in Colorado in a poultry worker who experienced mild illness in 2022.