The genetic analysis of the H5N1 avian flu virus in specimens from the nation’s first severely ill hospitalized patient in Louisiana reveals mutations that may enable upper-airway infection and greater transmission, concludes a technical summary from the Centers for Disease Control and Prevention (CDC).
But the authors of the report, released late yesterday afternoon, say the risk of an influenza pandemic amid the ongoing outbreak remains low.
In related news, Los Angeles County and Stanislaus County this week announced their first human H5N1 cases in two dairy workers. Both workers had mild symptoms and are recovering after receiving antiviral drugs. No related cases have been identified.
California, which has reported a total of 37 cases, recently announced a public health emergency for H5N1 to free up more resources with the virus now spreading to dairy farms beyond the Central Valley and further south.
The US total for human cases is now at 65.
Mutations likely occurred during viral replication in patient
CDC scientists compared H5N1 genomes in the virus infecting the Louisiana patient, who had contact with backyard poultry, with those of other H5N1 viruses from dairy cows, wild birds, poultry, and previous human patients.
The changes observed were likely generated by replication of this virus in the patient with advanced disease rather than primarily transmitted at the time of infection.
The causative viral genotype in the Louisiana patient was D1.1. The hemagglutinin (HA) sequences from the patient’s two respiratory specimens were closely related to those identified in other D1.1 viruses, including those sequenced from samples collected in November and December in wild birds and poultry in Louisiana.
The genotype is different from B3.13, the genotype causing outbreaks in animals such as dairy cows and poultry, with sporadic mild infections in dairy workers in the United States, the authors noted.
The viral mutations seen in the Louisiana case weren’t seen in viruses collected from poultry living on the patient’s property.
“It is important to note that these changes represent a small proportion of the total virus population identified in the sample analyzed (i.e., the virus still maintains a majority of ‘avian’ amino acids at the residues associated with receptor binding),” the authors wrote. “The changes observed were likely generated by replication of this virus in the patient with advanced disease rather than primarily transmitted at the time of infection.”
The researchers said that the mutations are rare in people and occur most often during severe infections. “One of the changes found was also identified in a specimen collected from the human case with severe illness detected in British Columbia, Canada, suggesting they emerged during the clinical course as the virus replicated in the patient,” they wrote. The British Columbian case was reported in November in a hospitalized teen.
No mutations in sequences facilitating adaptation to mammalian hosts or those tied to antimicrobial resistance were found.
Changes would be more concerning in animal
While the CDC noted that the findings are concerning and highlight the risk of H5N1 virus mutation during human infection, they would be more worrisome if they had been identified in an animal or within a few days after symptom onset, when they may be more likely to enable transmission to close contacts.
“Notably, in this case, no transmission from the patient in Louisiana to other persons has been identified,” the researchers wrote. “The Louisiana Department of Public Health and CDC are collaborating to generate additional sequence data from sequential patient specimens to facilitate further genetic and virologic analysis.”
The CDC urged ongoing genomic surveillance in people and animals, containment of H5N1 outbreaks in dairy cattle and poultry, and prevention measures among people exposed to infected animals or environmental settings.
Findings could be used in flu vaccine development
Michael Osterholm, PhD, MPH, director of the University of Minnesota’s Center for Infectious Disease Research and Policy (CIDRAP), publisher of CIDRAP News, concurred with the authors. He said it’s important to follow cases like this, but “even considering the case in British Columbia, which was also caused by the D.1 strain, it doesn’t change the risk picture for pandemic influenza in any way.”
These data indicate the viruses detected in respiratory specimens from this patient are closely related to existing HPAI A(H5N1) CVVs [candidate vaccine viruses] that are already available to manufacturers, and which could be used to make vaccines if needed.
The mutations have been seen in previous H5N1 cases and didn’t result in person-to-person transmission. But a flu pandemic will happen sometime in the future—with H5N1 or another virus—requiring the continued development and production of effective flu vaccines, he said.
The summary authors also commented on flu vaccine development. “These data indicate the viruses detected in respiratory specimens from this patient are closely related to existing HPAI A(H5N1) CVVs [candidate vaccine viruses] that are already available to manufacturers, and which could be used to make vaccines if needed,” they wrote.
In an X post, Angela Rasmussen, PhD, a virologist at the Vaccine and Infectious Disease Organization at the University of Saskatchewan in Canada, said, “There are low frequency mutations in HA that indicate adaptation in a human host—specifically this human host. But this doesn’t really change much in terms of estimating pandemic risk.”
