Research

What We Know—and Don’t Know—About H5N1 Bird Flu

Amid the unprecedented spread of the deadly avian influenza strain to cows and pasteurized milk, Jessica Leibler and David Hamer share their concerns about H5N1 and the actions that government officials and the public can take as the virus continues to evolve.

One month since the H5N1 strain of bird flu was first spotted in US dairy cows, fragments of the virus have been detected in commercial milk, increasing the already heightened concern among experts about the extent of the virus’ national and global spread, as well as its potential to mutate and spread to humans.

Should a zoonotic spillover occur and lead to human-to-human transmission, H5N1’s high fatality rate—at greater than 50 percent—could spark a pandemic much deadlier than COVID-19. But federal officials have reiterated it is unlikely that we are anywhere near that scenario, and with no evidence of person-to-person transmission, the current risk to the public remains low. 

Other strains of bird flu have caused previous outbreaks in the US and around the world, but the highly pathogenic H5N1 strain has caused unusually high levels of death among wild birds, before spreading to farmed poultry and mammals. Genetic data suggest that the latest outbreak among cattle spurred from a single wild bird-to-cow infection, progressing to cow-to-cow transmission perhaps months before the first identified dairy cow cases in March. 

The current H5N1 outbreak began spreading to US poultry farms, mammals, and marine life in late 2022. In the last year, H5N1 has killed or led to the euthanizing of tens of millions of wild and farmed birds, and in the last month, spread to more than 30 dairy cow herds in eight states. So far, only two people in the US have contracted H5N1—both farmworkers who were directly exposed to infected poultry or cattle—and both people have reported only mild symptoms, including pink eye and fatigue.

“While we are concerned about livestock health and production, the central concern is what this evolution of H5N1 to cow-to-cow transmission means for human exposure and for the virus’ capacity to evolve to human-to-human transmissible forms,” says Jessica Leibler, associate professor of environmental health, and who studies novel zoonotic viruses and antibiotic resistance to these viruses. 

Also troubling are the deepening criticisms from scientists who say the USDA and Food and Drug Administration are not sharing data about H5N1 spread or commercial milk safety quickly or thoroughly enough with scientists or the public, echoing the communication missteps that plagued the federal response to COVID-19. On April 19, the USDA shared raw data on H5N1 infections, but the data did not provide specific details about when samples were collected, or where the virus was spreading exactly—data that would be crucial for developing local, state, and regional safety and surveillance responses. 

The US may, however, be in a better position to treat bird flu with existing therapeutics that treat seasonal flu—but there are still many unknowns, such as how the virus will evolve and mutate, as well as whether the US (and globe) has the tools to mass-produce effective drugs to meet demand.

“There are national stockpiles of the currently available drugs, although I am not sure whether the quantities will be sufficient for a nationwide or global pandemic,” says Davidson Hamer, professor of global health and medicine at SPH and BU Chobanian and Avedisian School of Medicine, and a faculty member and former interim director of the Center on Emerging Infectious Diseases at BU. “There will be a need to rapidly scale up treatment.”

Hamer and Leibler discuss more about the history of H5N1, their concerns about current and future transmission, and the precautionary actions that both government officials and the public can take as the outbreak continues to unfold.

Information about H5N1 is evolving quickly. Responses reflect knowledge as of Friday morning, April 26.

The WHO’s chief scientist is now calling H5N1 a “global zoonotic animal pandemic.” What does that mean, and what is most concerning to you about this current global outbreak?

Jessica Leibler: H5N1 has circulated in wild bird species since at least the 1990s, with regular spillover into domesticated poultry production and occasionally mammal species, including humans, but the virus has not to date evolved to be easily transmissible among mammals. In recent months, there has been documented H5N1 spillover into dairy cattle with what appears to be significant transmission within and between dairy herds. The virus has also been found in other mammalian species, including seals, foxes, skunks and other wild mammals in the US, although there are to date only two documented cases in humans in the US during recent months. 

H5N1 is highly lethal to domesticated poultry, which has been its main source of distinction since its emergence, but has not successfully developed mechanisms for replicating and transmitting very well in mammals. The concern is that the spillover into dairy cows may indicate the virus is changing in ways that promote transmissibility in other mammals, including humans. 

Davidson Hamer: There are several different types of avian influenza but H5N1 has been the most commonly identified. During the last several decades, most of the transmission to humans has been from poultry, usually chickens, and has led to individual cases, or perhaps a few cases in the same family due to a common exposure. 

This strain of influenza can cause very severe disease with a high case fatality rate, but it has not evolved to become transmissible from human to human…or at least not yet.

How is bird flu primarily transmitted, and why has the recent spread to cows been particularly worrying?

Leibler: Bird flu is primarily transmitted through respiratory and fecal pathways. Wild birds are drawn to intensified animal operations, such as dairies or poultry farms, because there is often undigested animal food in animal manure/litter, which is not managed in a completely biosecure way, especially poultry waste. So these facilities are sometimes a food source for wild animals and an attraction to them, and if wild bird populations are infected with H5N1, they can introduce the virus to these domesticated livestock facilities.

Cows are an animal type where we don’t typically see influenza A viruses. They are different from pigs in that regard, which are very susceptible to many zoonotic influenza A viruses and have in the past served as “mixing vessels” for zoonotic influenza viruses that can or have become human pandemics. Cows haven’t typically served this role, although there is a novel influenza virus, influenza D, which was discovered in cows in the last 10 years, for which we see evidence of worker exposure. 

Typically, we think of influenza A viruses as the viruses with human pandemic potential, as these viruses infect different kinds of mammals and they are more likely to evolve in ways that allow for mammal-to-mammal transmission. A zoonotic virus that contains genetic elements specific to animal viruses but adapts to human-to-human transmission could result in a pandemic virus to which human immunity would be limited. This is the core concern around pandemic potential of zoonotic influenza A viruses.  

Influenza A viruses mutate rapidly, so the central concern right now is whether this H5N1 virus has evolved a mechanism to transmit between cows—which it appears it has—and whether intensified transmission among cows increases human exposure. Over the years, H5N1 has not to date evolved in a direction that has allowed for sustained human-to-human transmission, despite widespread human exposure from poultry. 

The USDA has received a lot of criticism for being slow to share critical data with researchers and the public. Is this a misstep on their part, and how can we avoid repeating the repeated communication failures during COVID? 

Hamer: Government agencies should be able to release accurate updates quickly including important information like virus sequences—which should be placed in public genetic repositories, as has become the norm for SARS-CoV-2. It is not clear why the USDA has delayed in doing so, but it may relate to internal bureaucratic practices that require special clearance before releasing data publicly or providing updates to the general public. One would think that these procedures would have been optimized during the COVID-19 pandemic.

Does the recent detection of virus particles in pasteurized milk raise alarm bells? Should there be widespread or routine testing of dairy cows, beyond the new testing requirements for interstate movement, to account for asymptomatic spread?

Hamer: Pasteurization of milk should inactivate the virus. If the virus fragments are being detected by polymerase chain reaction (PCR), this does not tell whether the virus is alive, or just inactive virus genetic material. One needs to do viral culture to determine whether there is live virus present. It is highly unlikely that the avian influenza virus would survive the pasteurization process.

So there is an increased risk of contracting H5N1 from consuming raw milk or undercooked eggs?

Leibler: Drinking raw or unpasteurized milk is never a good idea from a public health standpoint. Pasteurization is one of the great public health interventions that we take for granted now in our food system, as it protects us from pathogen exposure from dairy products. 

There is a good deal of evidence that H5N1 virus is expressed in milk from infected dairy cows, and milk could be a central pathway of the between-farm transmission we are seeing right now. But raw milk also can contain bacterial pathogens or perhaps more day-to-day concerns, like Salmonella, so it’s good to avoid raw milk more generally. 

Undercooked eggs pose many pathogen exposure risks, including bacteria and viruses, so thoroughly cooking eggs to 165 degrees is a good approach to reduce pathogen exposure from this source. The greatest risk from eggs in regard to H5N1 is probably for workers who are handling eggs from infected poultry, through fecal matter on the eggs directly—not to the consumer. 

Is it encouraging news that the symptoms in the two reported US human cases of H5N1 have been mild?

Hamer: As Dr. Leibler has noted, encountering H5N1 in cows is a new development. As the initially reported human cases were very mild, this is a good sign, although the fact that they appeared to have acquired the infection from cattle is worrisome as this form of influenza appears to be affecting even more species than in the past. It is surprising that these two human cases had such mild illness when past human cases of H5N1 were generally associated with severe disease and a substantial risk of death. One wonders whether there has been some form of attenuation of the pathogenicity of the virus as it has passed through cows.

Do you think we are in a good place with vaccine development and treatments, or do you worry that we could witness the same shortfalls in production—and inequities in access—as we did for COVID vaccines?

Hamer: We have decades of experience developing vaccines for influenza although these are not perfect tools. When there is a good match between circulating strains, based on hemagglutinin (H) and neuroaminidase (N), then their efficacy is relatively good. We should be able to scale up vaccines for a new H5N1 strain within a few months since we have the technology and experience to do so. Since there are multiple pharmaceutical companies that make influenza vaccines (a quick internet search identified 6 different companies), there is potential to rapidly scale up production with public-private partnerships. 

Making sure we address equities in access must be a focus if we have another pandemic. We need to use innovative strategies that were tested and shown to be effective to make sure there is equitable access to vaccines in high-, middle-, and low-income countries. 

We have neuroaminidase inhibitors, oseltamivir and zanamavir, that work fairly well to reduce symptoms and complications for patients with seasonal influenza and there is some evidence that these have activity against some strains of avian influenza. Ideally, we need better drugs that have even greater antiviral activity. 

The WHO recently updated its terminology for airborne transmission, now defining airborne pathogens as “infectious respiratory particles” rather than “aerosols” or “droplets.” How can this change in verbiage help improve how we communicate H5N1 updates to the public as the virus inevitably evolves?

Leibler: “Respiratory particles” is a broader term that encompasses both aerosols and droplets, which are particles of different sizes (aerosols are smaller particles than droplets). WHO is indicating that from an intervention perspective, we should assume both are infectious and take precautions to avoid human exposure. The message for food animal workers and industries across livestock production is that occupational respiratory protection at the most protective level—against bioaerosol exposure—is needed to protect human infection from this virus. 

Hamer: For individual protection during animal contact, I fully agree with Dr. Leibler about the need for respiratory protective equipment for anyone with an occupational exposure. If we have a major outbreak or pandemic, we will need to have widespread mask use as one of the major interventions to help reduce spread of the virus and for individual protection.