Older adults might be more resistant to bird flu infections than children, Penn research finds

Previous exposures to older flu strains prime the immune system to produce antibodies against H5N1, and children would likely benefit the most from H5N1 vaccinations

University of Pennsylvania School of Medicine

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PHILADELPHIA— Prior exposures to specific types of seasonal influenza viruses promote cross-reactive immunity against the H5N1 avian influenza virus, according to new research from the Perelman School of Medicine at the University of Pennsylvania. Older adults who were exposed to seasonal flu viruses that circulated prior to 1968 were found to be more likely to have antibodies that bind to the H5N1 avian flu virus. The findings, published today in Nature Medicine¸ suggest that younger adults and children would benefit more from H5N1 vaccines, even those not tailored specifically to the current strain circulating in birds and cattle.

“We know that early childhood influenza exposures can elicit immune responses that last a lifetime,” said senior author Scott Hensley, PhD, a professor of Microbiology. “We found that antibody responses that were primed by H1N1 and H3N2 viruses decades ago can cross-react to H5N1 avian viruses circulating today. Most of these cross-reactive antibodies cannot prevent infections, but they will likely limit disease if we have an H5N1 pandemic.”

Potential protection from a rapidly changing virus

H5N1 viruses have circulated in birds for many years, but a new version, called clade 2.3.4.4b H5N1 virus emerged more recently, and has since spread among cattle. This current H5N1 strain does not bind well to receptors in the human upper airway, but widespread circulation in mammals could lead to mutations that help the virus infect human airway cells and increase transmission. If this occurs, H5N1 could potentially start spreading from human to human.

Influenza viruses are covered with two lollipop-shaped proteins called hemagglutinin and neuraminidase, for which the viruses are named (H5N1, for example). These proteins are what allows a virus to attach to “healthy” cells and start the process of infection. Current influenza vaccines primarily elicit antibodies that recognize hemagglutinin proteins, and prevent them from infecting a person’s cells. The lollipop “heads” of hemagglutinin proteins evolve more frequently while the “sticks” of the hemagglutinin lollipops, called stalks, don’t evolve as quickly. 

Researchers tested blood samples from over 150 people born between 1927 and 2016 for antibodies targeting the stalk proteins of different influenza viruses, including H5N1. They found that blood samples from older adults born prior to 1968 who were likely first exposed to H1N1 or H2N2 in childhood had higher levels of antibodies that could bind to the stalk of the H5N1 virus. They found that an individual’s birth year was closely linked to the amount of H5N1-fighting antibodies in their blood. Young children who were not exposed to seasonal flu viruses possessed low levels of antibodies that could fight H5N1.

Existing vaccines are effective

To determine how individuals with different birth years respond to H5N1 vaccinations, researchers obtained blood samples from a separate group of individuals born between 1918 and 2003 before and after they were vaccinated with a 2004 H5N1 vaccine that did not perfectly match the clade 2.3.4.4b H5N1 virus that is currently circulating.

Consistent with the researchers’ initial findings, older adults had higher amounts of antibodies that could bind to H5 stalks before vaccination.  Following vaccination, H5 stalk antibodies increased slightly in older adults, but increased substantially in children. These antibodies bound to both the 2004 H5N1 virus and to the clade 2.3.4.4b H5N1 virus that is circulating today.

“In the event of an H5N1 pandemic, all age groups will likely be highly susceptible, but it is possible that the highest disease burden will be in children,” said Hensley. “If this is the case, children should be prioritized for H5N1 vaccinations.”

This research was supported by the National Institute of Allergy and Infectious Diseases (75N93021C00015, R01AI08686).

 

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Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.   

The Perelman School of Medicine is consistently among the nation's top recipients of funding from the National Institutes of Health, with $580 million awarded in the 2023 fiscal year. Home to a proud history of “firsts” in medicine, Penn Medicine teams have pioneered discoveries and innovations that have shaped modern medicine, including recent breakthroughs such as CAR T cell therapy for cancer and the Nobel Prize-winning mRNA technology used in COVID-19 vaccines.

The University of Pennsylvania Health System’s patient care facilities stretch from the Susquehanna River in Pennsylvania to the New Jersey shore. These include the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Chester County Hospital, Lancaster General Health, Penn Medicine Princeton Health, and Pennsylvania Hospital—the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.  

Penn Medicine is an $11.9 billion enterprise powered by more than 48,000 talented faculty and staff.   

  

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Journal

Nature Medicine

DOI

10.1038/s41591-025-03599-6 

Method of Research

Experimental study

Subject of Research

Human tissue samples

Article Title

Immune history shapes human antibody responses to H5N1 influenza viruses

Article Publication Date

13-Mar-2025

 

Immunity to seasonal flu protects against severe illness from bird flu in ferrets

A study in ferrets — which have remarkably similar respiratory systems to humans — suggests that widespread immunity to H1N1 seasonal influenza virus may explain why exposure to H5N1 bird flu causes only mild symptoms in humans

Penn State

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UNIVERSITY PARK, Pa. — The fatality rate for H5N1 highly pathogenic avian influenza in humans historically has been high, with more than half of people dying. Why, then, is the current H5N1 bird flu outbreak — which has caused massive die-offs in wild birds, farmed poultry and even wild mammals — causing mostly mild symptoms in the people it has infected? New research, led by scientists at Penn State and the University of Pittsburgh and published today (July 23) in the journal Science Translational Medicine, indicates that immunity to a seasonal influenza virus known as pandemic H1N1 that began circulating in 2009, provides protection from severe illness from H5N1 in a laboratory animal model.

“Every person has been exposed to H1N1 as the virus caused a pandemic in 2009 and is now the predominant circulating influenza strain in 1 out of every 3-4 years” said lead author Troy Sutton, associate professor of veterinary and biomedical sciences at Penn State. “Our findings suggest that this immunity is protective against the more recent H5N1 strain and may explain why we’re seeing fewer cases and less severe disease than we would expect.”

H5N1 viruses from clade 2.3.4.4b emerged in 2020 and were carried around the world by wild migratory birds, where they have since infected farmed poultry, wild mammals and, most recently, dairy cattle. As of June 2025, 70 human cases of H5N1 have been confirmed in the United States with one death. Most of the individuals were exposed to dairy cows or poultry and exhibited mild symptoms of conjunctivitis, fever and cough, among others. By contrast, previous human infections with H5N1 resulted in far more severe symptoms, such as seizures and respiratory failure, and some infected people died from the infection or related complications.  

"We wanted to know why H5N1 2.3.4.4b was not causing severe outcomes so we investigated whether pre-existing immunity to seasonal influenza could be providing protection," said Katherine Restori, assistant research professor of veterinary and biomedical sciences, Penn State. Restori explained that this research was conducted in ferrets, which are widely recognized as one of the best animal models for studying influenza virus infections.

To conduct their study, Sutton and his colleagues, including Valerie LeSage, research assistant professor, University of Pittsburgh, who co-led the research, studied ferrets with immunity to three common types of seasonal flu: Influenza B, H1N1 and H3N2. They also studied a control group of ferrets that had no immunity to flu. Ninety days after infecting the ferrets with these common seasonal flu viruses, the team confirmed immunity by testing the animals’ blood for antibodies. Next, the team exposed the ferrets through an inoculation in the nose to a version of the H5N1 virus that caused an outbreak on mink farms in Spain in 2022.

They found that all the ferrets without immunity to the seasonal flu viruses, as well as those with immunity to Influenza B, became sick, lost weight and reached a humane endpoint. The H3N2-immune ferrets lost 10% of their body weight but all survived. In contrast, the ferrets with immunity to H1N1 did not lose any weight and all survived.

Next, the team studied the potential protective effects of the same three seasonal influenza viruses against the more recent H5N1 virus that has been circulating in dairy cattle. This time, instead of inoculating the ferrets with H5N1 in the nose, the team exposed ferrets with immunity to H1N1, H3N2, or without immunity to a seasonal virus, to ferrets already infected with an H5N1 virus from dairy cows. Sutton said by examining exposure to H5N1-infected ferrets, the team could assess the transmissibility of the virus in addition to the effects of pre-existing immunity.

The researchers found that upon exposure to ferrets with dairy cow H5N1 infections, ferrets without any influenza immunity rapidly developed severe and lethal disease. When exposed to H5N1-infected ferrets, all the ferrets with pre-existing immunity to H3N2 became infected and replicating H5N1 virus was detected in their noses. These ferrets lost weight and half of them reached a humane endpoint. In contrast, only half of the ferrets previously infected with the 2009 H1N1 virus became infected, and the infected animals were protected against disease and had very low levels of viral replication in the nose.

“These findings demonstrate that pre-existing immunity to the 2009 H1N1 virus or H3N2 virus reduces the severity of H5N1 disease, with H1N1 providing even greater protection than H3N2,” Sutton said. “This study provides a potential explanation for the mostly mild disease we are seeing in humans, as humans already have immunity to H1N1.” However, Sutton noted, as the H5N1 virus continues to circulate in animals, it has opportunities to evolve to become more dangerous.

Experiments using the mink H5N1 and dairy cattle H5N1 viruses were performed in Penn State’s biosafety level 3 Eva J. Pell Laboratory for Advanced Biological Research. This facility is approved by the Centers for Disease Control and Prevention and United States of Department of Agriculture for work with highly pathogenic avian influenza. All experiments were performed in compliance with all local, state and federal rules and regulations.

Other Penn State authors on the paper include Veronika Weaver, research technologist; Devanshi Patel, graduate student; Kayla Septer, graduate student; Cassandra Field, graduate student; Michael J. Bernabe, graduate student; Ethan Kronthal, graduate student; Allen Minns, research technician; and Scott Lindner, associate professor of biochemistry and molecular biology. Grace Merrbach, laboratory research technician, University of Pittsburgh, and Seema Lakdawala, associate professor of microbiology and immunology, Emory University, also are authors of the paper.

The National Institutes of Health, Centers of Excellence for Influenza Research and Response (CEIRR) and United States of Department of Agriculture supported this research.

At Penn State, researchers are solving real problems that impact the health, safety and quality of life of people across the commonwealth, the nation and around the world. 

For decades, federal support for research has fueled innovation that makes our country safer, our industries more competitive and our economy stronger. Recent federal funding cuts threaten this progress. 

Learn more about the implications of federal funding cuts to our future at Research or Regress.  

 

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Journal

Science Translational Medicine

DOI

10.1126/scitranslmed.adw4856 

 

Review shows bird flu control strategies ‘not working’

Gaps in data highlight potential for silent spread

The Pirbright Institute

 

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A review of sustained mammal-to-mammal bird flu transmission in diverse species, led by The Pirbright Institute, shows global control strategies are not working.

Writing in Nature, researchers analysed whether outbreaks in European fur farms, South American marine mammals and United States dairy cattle raise questions about whether humans are next. Led by zoonotic influenza specialist Dr Thomas Peacock, the scientists evaluated how recent changes in the ecology and molecular evolution of H5N1 in wild and domestic birds increase opportunities for spillover to mammals.

They also weighed various evolutionary pathways that could turn the global H5N1 influenza panzootic into a human pandemic virus.

“Influenza A viruses (IAV) have caused more documented global pandemics in human history than any other pathogen. Historically, swine are considered optimal intermediary hosts that help avian influenza viruses adapt to mammals before jumping to humans,” said Dr Peacock, who investigates the drivers of the current H5N1 avian influenza panzootic. “However, the altered ecology of H5N1 has opened the door to new evolutionary pathways.”

The review highlights potential gaps in control mechanisms, including a reluctance to engage with modern vaccine and surveillance technologies and a dearth of data collection around the transmission of H5N1 between cows and to humans on US dairy farms.

Whilst previous generations of US cattle producers had eradicated foot-and-mouth disease by rapidly sharing epidemiological data, the authors say months of missing data is leaving researchers, veterinarians, and policy makers in the dark.

“H5N1 is a reportable disease in poultry, but not mammals, in the US. The US Department of Agriculture requires H5N1 testing only in lactating cattle prior to interstate movement,” said Dr Peacock.

Current practices for H5N1 testing in wildlife focus on carcasses, not monitoring animals whilst alive, the paper notes, providing opportunities for variants of H5N1 to spread silently undetected.

“What keeps scientists up at night is the possibility of unseen chains of transmission silently spreading through farm worker barracks, swine barns, or developing countries, evolving under the radar because testing criteria are narrow, government authorities are feared, or resources are thin.”

An evolutionary process of “genomic reassortment” in viruses with segmented genomes is driving the global panzootic outbreak. When two or more viruses co-infect a single host, they can swap entire segments during genome replication to create novel hybrids.

The reassortment between H5N8 and low pathogenicity avian influenza (LPAI) viruses that generated the panzootic H5N1 virus in the Americas is believed to have occurred in Europe or central Asia around 2020, infecting South American marine mammals and US dairy cattle.

The writers say the prospect of H5N1 becoming continually present in Europe and the Americas is a turning point for High Pathogenicity Avian Influenza (HPAI).

“New control strategies are needed, including vaccination. Influenza vaccines are licensed for poultry that reduce disease burden, but do not prevent infection and have varying degrees of success.”

Stocks of H5 vaccine that are antigenically related to circulating viruses are available and could be produced at scale using mRNA platforms if H5N1 begins spreading in humans, the authors note.

“The severity of a future H5N1 pandemic remains unclear. Recent human infections with H5N1 have a substantially lower case fatality rate compared to prior H5N1 outbreak in Asia, where half of people with reported infections died. The lack of severity in US cases may be due to infection through the eye, rather than through viral pneumonia in the lung.”

Older people appear to have partial immunity to H5N1 due to childhood exposure, whereas younger people born since the 1968 H3N2 pandemic may be more susceptible to severe disease in a H5N1 pandemic.

Dr Peacock’s work is funded by UKRI Biotechnology and Biological Sciences Research Council (BBSRC) via the Pirbright Institute’s Strategic Programme Grants (ISPGs)  and the UK Medical Research Council / Department for Environment, Food and Rural Affairs FluTrailMap One Health consortium, and the BBSRC/DEFRA ‘FluTrailMap’ consortium.

Read the Paper: https://www.nature.com/articles/s41586-024-08054-z

DOI: 10.1038/s41586-024-08054-z

 

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Journal

Nature

DOI

10.1038/s41586-024-08054-z 

Method of Research

Literature review

Article Title

The global H5N1 panzootic in mammals

Article Publication Date

24-Sep-2024

 

The H5N1 influenza outbreaks in the US dairy cattle likely triggered by the "milk-stealing" behavior of lactating cows

Science China Press

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How the H5N1 virus invades the mammary gland of dairy cattle

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Credit: ©Science China Press

H5N1 highly pathogenic avian influenza poses a serious threat to both animal and human health. Since 2021, a novel H5N1 virus has caused thousands of outbreaks among poultry and wild birds across multiple countries. In March 2024, H5N1 virus was first reported in dairy cattle in the United States. As of June 2025, outbreaks have been reported on more than 1,070 dairy farms across 17 states, with a mortality rate of up to 10% in affected cattle. Moreover, 41 dairy farm workers were infected by the virus, highlighting a significant threat to the global dairy industry and public health. The H5N1 virus causes severe lesions in the mammary glands and contaminates milk, with H5N1 viral genes detected in 25% of retail milk samples in the U.S. However, as a typical respiratory pathogen, how does the H5N1 virus enter the mammary glands of dairy cows? A Chinese research team led by Professor Hualan Chen has solved this mystery, and they also provide a strategy on how to control the disease in cattle.

The scientists performed this study by using a total of 50 cattle, including 46 lactating cows and four calves, in the animal biosafety level 3+ (P3+) facility at the Harbin Veterinary Research Institute. They extensively investigated the replication, tissue tropism, and pathogenicity of H5N1 virus in cattle after different route inoculation, and they found that virus delivered into the nose can only replicate in tissues of the mouth and respiratory tract of the cattle, and virus inoculated into the mammary gland replicates only in the inoculated gland but does not migrate to neighboring mammary glands of the cattle, suggesting that entry through the teat is the only natural way the virus can infect the mammary glands of cattle.

Given that some lactating cows’ "steal milk" through self-nursing or mutual-nursing, they speculated that "mouth-to-teat" transmission may be the route by which the H5N1 virus initially infects the mammary glands of dairy cows. They found that bovine oral tissues express high levels of sialic acid receptors, which favors viral infection through contaminated feed and water, and explains why the H5N1 virus could replicate efficiently in the oral cavity and be released for several days. They further demonstrated that H5N1 virus in the oral cavity of calves could be successfully transmitted to the mammary glands of the lactating cows they sucked. 

Vaccination has been a strategy for control of highly pathogenic avian influenza in poultry in China and several other countries, but it is unknown whether vaccination also prevents H5N1 influenza infection in cattle. They tested two vaccines in lactating cattle, and demonstrated that both H5 inactivated vaccine and hemagglutinin-based DNA vaccine conferred complete protection against H5N1 infection in cattle, even after a high-dose of virus challenge via direct intramammary gland inoculation.

“This study not only provides crucial insights into controlling the ongoing cattle H5N1 influenza in the United States,” said Hualan Chen, a renowned virologist and the leader of this study, “but also offers scientific suggestions on how to prevent the H5N1 influenza outbreak in dairy cattle in other countries”.

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Journal

National Science Review

DOI

10.1093/nsr/nwaf262/8180392 

Method of Research

Experimental study

 

NIH officials assess threat of H5N1

Balancing enhanced vigilance and “business as usual”

NIH/National Institute of Allergy and Infectious Diseases

 

image: 

Photo of a wild bird. To the right is a colorized transmission electron micrograph of H5N1 virus particles (purple). H5N1 bird flu is widespread in wild birds worldwide, and in 2024 is causing a multistate outbreak in poultry and U.S. dairy cows. Bird photo by NIAID; micrograph, which has been repositioned and recolored by NIAID, is courtesy CDC. 

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Credit: NIAID and CDC

WHAT:
Highly pathogenic H5N1 avian influenza A virus (HPAI H5N1) remains a low risk to the general public, and public health experts in the United States believe that available treatments and vaccines, as well as those in development, are sufficient to prevent severe disease. However, the National Institutes of Health (NIH) and its federal partners remain focused on monitoring the virus and evaluating changes, according to leading officials at the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH. 

In a commentary published in the New England Journal of Medicine, NIAID Director Jeanne M. Marrazzo, M.D., M.P.H., and Michael G. Ison, M.D., M.S., chief of the Respiratory Diseases Branch in NIAID’s Division of Microbiology and Infectious Diseases, say people should find a balance between enhanced vigilance and “business as usual” with respect to HPAI H5N1.

Since 1996, HPAI H5N1 influenza viruses have circulated in at least 23 countries. In late 2021, HPAI H5N1 spread from Europe to North America causing sporadic infections among wild birds and poultry farms. In 2022, the virus spread to South America where it devastated birds and marine mammals. In March 2024, USDA scientists identified HPAI H5N1 in U.S. dairy cows, and it subsequently reached herds in 16 states. The virus has been detected in dairy herds in three states over the past 30 days, according to USDA/APHIS. In 2024, the virus has caused 66 confirmed and 7 probable cases of influenza in people in the U.S. and one case in Canada. These human cases have been caused by either the H5N1 type circulating in birds (D1.1) or the type circulating in dairy cows (B3.13).

Against this backdrop, Drs. Marrazzo and Ison say there are four keys to controlling the current outbreak. The first imperative is timely, effective collaborations among investigators in human and veterinary medicine, public health, health care, and occupational workers, such as dairy and poultry workers.

This involves cultivating trust not only between numerous entities, but with people seeking care for symptoms of concern, including conjunctivitis, the authors write. Fortunately, so far most U.S. cases of HPAI H5N1 have been mild and resolved on their own without the need for treatment.

Their second key is a focus on the Canadian HPAI H5N1 patient, who developed respiratory failure and required life-saving medical intervention and treatment before recovering. The authors write that mutations found in the virus in this patient highlight an urgent need for vigilant disease surveillance to identify and assess viral changes to evaluate the risk for person-to-person transmission. Effective surveillance, they say, requires that complete genomic sequencing data from animals and people are made rapidly and readily available.

Without information pertaining to where and when isolates were collected, the data cannot be linked phylogenetically to other reported sequences, limiting insight into how the virus is spreading, they write. These data would also provide opportunity for early detection of mutations that might portend avidity for human respiratory epithelium, which may require as little as one mutation in the virus.

Third, researchers must continue to develop and test medical countermeasures—such as vaccines and therapies that eliminate or alleviate disease—against H5N1 and other influenza viruses. Fortunately, current vaccine candidates neutralize the circulating strains, which so far are susceptible to antivirals that could mitigate transmission and severity of illness, they write.

Lastly, Drs. Marrazzo and Ison encourage people to take precautions to prevent exposure to the virus and minimize the risk of infection. For example, people who work with poultry and cows should use personal protective equipment and educate themselves about occupational risks when working with birds and mammals, as CDC and USDA have repeatedly recommended.

Ideally, following these four steps will help scientists and public health officials investigating HPAI H5N1 to answer the many remaining questions more quickly about how the virus is spreading, evolving, and affecting people, other mammals, and birds.

ARTICLE:
M Ison and J Marrazzo. The Emerging Threat of H5N1 to Human Health. NEJM DOI: 10.1056/NEJMe2416323 (2024).

WHO:
NIAID Director Jeanne M. Marrazzo, M.D., M.P.H., and Michael G. Ison, M.D., M.S., chief of the Respiratory Diseases Branch in NIAID’s Division of Microbiology and Infectious Diseases, are available for comment. 

CONTACT:
To schedule interviews, please contact Ken Pekoc, (301) 402-1663, kpekoc@niaid.nih.gov.

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NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.
  
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov/.

NIH...Turning Discovery Into Health®

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Journal

New England Journal of Medicine

DOI

10.1056/NEJMe2416323 

Article Title

The Emerging Threat of H5N1 to Human Health

Article Publication Date

31-Dec-2024

Bird Flu Is Bad for Poultry and Dairy Cows. It’s Not a Dire Threat for Most of Us — Yet.

2024/05/03

Headlines are flying after the Department of Agriculture confirmed that the H5N1 bird flu virus has infected dairy cows around the country. Tests have detected the virus among cattle in nine states, mainly in Texas and New Mexico, and most recently in Colorado, said Nirav Shah, principal deputy director at the Centers for Disease Control and Prevention, at a May 1 event held by the Council on Foreign Relations.

A menagerie of other animals have been infected by H5N1, and at least one person in Texas. But what scientists fear most is if the virus were to spread efficiently from person to person. That hasn’t happened and might not. Shah said the CDC considers the H5N1 outbreak “a low risk to the general public at this time.”

Viruses evolve and outbreaks can shift quickly. “As with any major outbreak, this is moving at the speed of a bullet train,” Shah said. “What we’ll be talking about is a snapshot of that fast-moving train.” What he means is that what’s known about the H5N1 bird flu today will undoubtedly change.

With that in mind, KFF Health News explains what you need to know now.

Q: Who gets the bird flu?

Mainly birds. Over the past few years, however, the H5N1 bird flu virus has increasingly jumped from birds into mammals around the world. The growing list of more than 50 species includes seals, goats, skunks, cats, and wild bush dogs at a zoo in the United Kingdom. At least 24,000 sea lions died in outbreaks of H5N1 bird flu in South America last year.

What makes the current outbreak in cattle unusual is that it’s spreading rapidly from cow to cow, whereas the other cases — except for the sea lion infections — appear limited. Researchers know this because genetic sequences of the H5N1 viruses drawn from cattle this year were nearly identical to one another.

The cattle outbreak is also concerning because the country has been caught off guard. Researchers examining the virus’s genomes suggest it originally spilled over from birds into cows late last year in Texas, and has since spread among many more cows than have been tested. “Our analyses show this has been circulating in cows for four months or so, under our noses,” said Michael Worobey, an evolutionary biologist at the University of Arizona in Tucson.

Q: Is this the start of the next pandemic?

Not yet. But it’s a thought worth considering because a bird flu pandemic would be a nightmare. More than half of people infected by older strains of H5N1 bird flu viruses from 2003 to 2016 died. Even if death rates turn out to be less severe for the H5N1 strain currently circulating in cattle, repercussions could involve loads of sick people and hospitals too overwhelmed to handle other medical emergencies.

Although at least one person has been infected with H5N1 this year, the virus can’t lead to a pandemic in its current state. To achieve that horrible status, a pathogen needs to sicken many people on multiple continents. And to do that, the H5N1 virus would need to infect a ton of people. That won’t happen through occasional spillovers of the virus from farm animals into people. Rather, the virus must acquire mutations for it to spread from person to person, like the seasonal flu, as a respiratory infection transmitted largely through the air as people cough, sneeze, and breathe. As we learned in the depths of covid-19, airborne viruses are hard to stop.

That hasn’t happened yet. However, H5N1 viruses now have plenty of chances to evolve as they replicate within thousands of cows. Like all viruses, they mutate as they replicate, and mutations that improve the virus’s survival are passed to the next generation. And because cows are mammals, the viruses could be getting better at thriving within cells that are closer to ours than birds’.

The evolution of a pandemic-ready bird flu virus could be aided by a sort of superpower possessed by many viruses. Namely, they sometimes swap their genes with other strains in a process called reassortment. In a study published in 2009, Worobey and other researchers traced the origin of the H1N1 “swine flu” pandemic to events in which different viruses causing the swine flu, bird flu, and human flu mixed and matched their genes within pigs that they were simultaneously infecting. Pigs need not be involved this time around, Worobey warned.

Q: Will a pandemic start if a person drinks virus-contaminated milk?

Not yet. Cow’s milk, as well as powdered milk and infant formula, sold in stores is considered safe because the law requires all milk sold commercially to be pasteurized. That process of heating milk at high temperatures kills bacteria, viruses, and other teeny organisms. Tests have identified fragments of H5N1 viruses in milk from grocery stores but confirm that the virus bits are dead and, therefore, harmless.

Unpasteurized “raw” milk, however, has been shown to contain living H5N1 viruses, which is why the FDA and other health authorities strongly advise people not to drink it. Doing so could cause a person to become seriously ill or worse. But even then, a pandemic is unlikely to be sparked because the virus — in its current form — does not spread efficiently from person to person, as the seasonal flu does.

Q: What should be done?

A lot! Because of a lack of surveillance, the U.S. Department of Agriculture and other agencies have allowed the H5N1 bird flu to spread under the radar in cattle. To get a handle on the situation, the USDA recently ordered all lactating dairy cattle to be tested before farmers move them to other states, and the outcomes of the tests to be reported.

But just as restricting covid tests to international travelers in early 2020 allowed the coronavirus to spread undetected, testing only cows that move across state lines would miss plenty of cases.

Such limited testing won’t reveal how the virus is spreading among cattle — information desperately needed so farmers can stop it. A leading hypothesis is that viruses are being transferred from one cow to the next through the machines used to milk them.

To boost testing, Fred Gingrich, executive director of a nonprofit organization for farm veterinarians, the American Association of Bovine Practitioners, said the government should offer funds to cattle farmers who report cases so that they have an incentive to test. Barring that, he said, reporting just adds reputational damage atop financial loss.

“These outbreaks have a significant economic impact,” Gingrich said. “Farmers lose about 20% of their milk production in an outbreak because animals quit eating, produce less milk, and some of that milk is abnormal and then can’t be sold.”

The government has made the H5N1 tests free for farmers, Gingrich added, but they haven’t budgeted money for veterinarians who must sample the cows, transport samples, and file paperwork. “Tests are the least expensive part,” he said.

If testing on farms remains elusive, evolutionary virologists can still learn a lot by analyzing genomic sequences from H5N1 viruses sampled from cattle. The differences between sequences tell a story about where and when the current outbreak began, the path it travels, and whether the viruses are acquiring mutations that pose a threat to people. Yet this vital research has been hampered by the USDA’s slow and incomplete posting of genetic data, Worobey said.

The government should also help poultry farmers prevent H5N1 outbreaks since those kill many birds and pose a constant threat of spillover, said Maurice Pitesky, an avian disease specialist at the University of California-Davis.

Waterfowl like ducks and geese are the usual sources of outbreaks on poultry farms, and researchers can detect their proximity using remote sensing and other technologies. By zeroing in on zones of potential spillover, farmers can target their attention. That can mean routine surveillance to detect early signs of infections in poultry, using water cannons to shoo away migrating flocks, relocating farm animals, or temporarily ushering them into barns. “We should be spending on prevention,” Pitesky said.

Q: OK it’s not a pandemic, but what could happen to people who get this year’s H5N1 bird flu?

No one really knows. Only one person in Texas has been diagnosed with the disease this year, in April. This person worked closely with dairy cows, and had a mild case with an eye infection. The CDC found out about them because of its surveillance process. Clinics are supposed to alert state health departments when they diagnose farmworkers with the flu, using tests that detect influenza viruses, broadly. State health departments then confirm the test, and if it’s positive, they send a person’s sample to a CDC laboratory, where it is checked for the H5N1 virus, specifically. “Thus far we have received 23,” Shah said. “All but one of those was negative.”

State health department officials are also monitoring around 150 people, he said, who have spent time around cattle. They’re checking in with these farmworkers via phone calls, text messages, or in-person visits to see if they develop symptoms. And if that happens, they’ll be tested.

Another way to assess farmworkers would be to check their blood for antibodies against the H5N1 bird flu virus; a positive result would indicate they might have been unknowingly infected. But Shah said health officials are not yet doing this work.

“The fact that we’re four months in and haven’t done this isn’t a good sign,” Worobey said. “I’m not super worried about a pandemic at the moment, but we should start acting like we don’t want it to happen.”

© Kaiser Health News