“There appears to be a gap in public confidence when it comes to the national response to bird flu."
Sarah Clark, MPH, Associate Research Scientist, Department of Pediatrics, University of Michigan
“To effectively address these gaps, pandemic preparedness initiatives should be urgently resourced and implemented.”
Jesse Goodman, MD, Center on Medical Product Access, Safety and Stewardship, Georgetown University Medical Center, Washington, D.C.
Influenza A (H1N1) is the virus that caused the 1918-1920 influenza pandemic—the so-called “mother of all pandemics”—and killed an estimated 50-100 million people globally. Influenza A H5N1 (“bird flu”) is another influenza A subtype virus that has been circulating among birds since 1996 and in 1997, caused the first human case of infection. In the early years of H5N1 outbreaks among humans, the mortality rate was approximately 50%. Given this high mortality rate, it’s no wonder that many epidemiologists are worried that bird flu has the potential of causing the next human pandemic.
In this week’s post, I summarize some key facts about seasonal flu and pandemic flu—the two different types of influenza A that plague humans. I also provide my opinion on whether H5N1 should be dealt with as a pandemic.
Seasonal influenza. A, B, C, and D are the four types of influenza viruses. All are RNA viruses, and built into each genome is the ability to mutate. Of these four influenza viruses, influenza A is by far the most common and destructive. It can infect a variety of animals including birds, pigs, and humans. In humans, it is responsible for seasonal flu which descends upon those of us living in the Northern Hemisphere mainly in September through April each year. Because of its ability to mutate, influenza A is a challenging adversary requiring that new vaccines be devised each year to help defend the human host against the virus.
The flu is primarily a respiratory tract infection. Its main symptoms are dry cough, sore throat, nasal congestion, fever, tiredness, and muscle aches. Although many cases of seasonal flu are relatively mild, it kills about 50,000 people per year in the U.S. When deaths occur, the lower respiratory tract (pneumonia) is most often involved.
Influenza A strains are subtyped by two proteins on its surface: H (hemagglutinin) and N (neuraminidase). This season, H1N1 and H3N2 subtypes have been the cause of most flu cases. According to the Centers for Disease Control and Prevention (CDC), the flu season this year has hit its highest severity since 2017-2018. For several months this year, the flu filled hospitals with severely ill patients, and in January 2025, for the first time since the beginning of the COVID-19 pandemic, more people in the U.S. died of the flu than of COVID-19.
The reasons for the 15-year high in flu mortality this season is not totally clear. Whether the seasonal flu vaccine this year is less effective than expected is unknown. What role low vaccination rates may be playing in seasonal flu cases is yet to be determined. And while antiviral medications (Tamiflu and Baloxivir) if taken early in the course of infection appear to cut the risk of death in older adults, it is also unclear what percentage of adults has access to these medications.
Pandemic influenza. Pandemic influenza is defined as “a global outbreak of a new flu A virus for which most of the human population has little or no immunity allowing for rapid and widespread transmission.” Since 1900, there have been four influenza pandemics:
1918-1920—The "Spanish Flu" pandemic, caused by influenza A(H1N1);
1957-1958—The "Asian Flu" pandemic, caused by influenza A(H2N2);
1968-1969—The "Hong Kong Flu" pandemic, caused by influenza A(H3N2); and
2009-2010—The "2009 influenza A(H1N1) pandemic" (often referred to as the "Swine Flu").
What about bird flu? As you can see, “bird flu,” influenza A H5N1, doesn’t qualify as a cause of pandemic influenza as it hasn’t had the “required” impact on the human population But, if we weren’t so anthropocentric (human-centered), H5N1 would easily meet the criteria as a pandemic flu.
Jeremy Farrar, chief scientist at the World Health Organization, called the ongoing spread of H5N1 “a pandemic of animals.” (See, “Will Bird Flu Evolve into the Next Human Pandemic?,” Germ Gems, January 15, 2025.) Since October 2021, at least 280 million birds (poultry and wildlife) have succumbed to H5N1. In addition to impacting 485 bird species, 48 mammal species have been targeted, including, most notably, cattle and pets. (Cats are especially susceptible with a mortality rate of 67%.)
In contrast, to date the case and mortality rates of H5N1 in humans have remained surprisingly (and thankfully) low. Of the 68 cases of human avian flu cases identified in the U.S. since 2024, there’s been only one death — an older adult in Louisiana who was infected by a bird in a backyard flock or poultry. And on February 15, 2025, only the fourth patient hospitalized with H5N1, a farmer from Ohio, was released from the hospital.
A major reason that H5N1 hasn’t evolved into a pandemic, at least not yet, is because the virus lacks the virulence factor that would permit its transmission from person to person. A broader understanding, however, of “the molecular mechanisms that underlie H5N1 receptor binding evolution is urgently needed to understand the drivers of this adaptation and to develop targeted interventions.” (See, “Evolving H5N1 receptor specificity,” Science, March, 2025.) As the authors of this section letter wrote: “The evolving receptor binding specificity of H5N1viruses constitutes an imminent public health risk that demands immediate international attention and collaborative research.”
How long will the H5N1 “pre-pandemic” status last? No one knows how long the H5N1 “pre-pandemic” status will last. If the H5N1 virus were to develop the mutation that allows it to be transmitted easily between humans, influenza A H5N1 will quickly acquire pandemic status.
Were this to occur, we can’t claim to be totally blindsided. For years, many epidemiologists and public health experts have been warning of a looming bird flu pandemic. Have we heeded this warning?
It appears that the current U.S. President’s administration has not. This administration’s mass firing of scientists and public health experts at the CDC and elsewhere threatens to undermine our nation’s ability to identify and control infectious disease outbreaks as well as our ability to develop new vaccines.
Despite this, highly knowledgeable and committed professionals have sustained their involvement in preparing for a potential bird flu pandemic. (See, J. Goodman, et. al, “Prepare now for a potential H5N1 pandemic,” Science March 5, 2025). In addition, it is reassuring to see some progress is being made to protect poultry against this virus. (See, “US gives conditional nod to Zoetis’ bird flu vaccine for poultry,” Reuters, February 14, 2025.) Nonetheless, if the pandemic unfolds, the question will be whether the U.S. still has the scientists, doctors, and public health experts at the CDC and elsewhere that are needed to address the bird flu crisis. I certainly hope so.
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